ESTRO 36 Abstract Book

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S325 ESTRO 36 2017
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% and 64 % and I5,30% values between 22 % to 50 %.
Conclusion
In this cohort, the comparison of GTV, GTV’ and V PET
volumes suggests that 18F-FDOPA PET images can be useful
for predicting tumor recurrence areas in half of the
patients with encouraging sensibility and sensitivity
values. As a next step, ROC curves will be calculated to
define the optimal SUV threshold for radiotherapy
delineation purpose. The analysis of all post-treatment MR
images will be conducted to better determine the starting
points of the recurrence and correlate them to the 18F-
FDOPA PET information.
PO-0629 A 4-miRNA signature predicts the therapeutic
outcome of glioblastoma
M. Niyazi 1,2,3, A. Pitea3,4 , M. Mittelbronn5, J. Steinbach 6,
C. Sticht7, F. Zehentmayr1,8, D. Piehlmaier3,4, H.
Zitzelsberger3,4, K. Lauber1,3, U. Ganswindt1,3, C. Rödel9,
C. Belka1,2,3, K. Unger3,4
1 LMU Munich, Department of Radiation Oncology,
Munich, Germany
2 German Cancer Research Center DKFZ, German Cancer
Consortium DKTK, Heidelberg, Germany
3 Helmholtz Zentrum München, Clinical Cooperation
Group Personalized Radiotherapy in Head and Neck
Cancer, Munich, Germany
4 Helmholtz Zentrum Muenchen - German Research
Center for Environmental Health, Research Unit
Radiation Cytogenetics, Muenchen, Germany
5 Goethe-University Frankfurt, Institute of Neurology
Edinger Institute, Frankfirt/Main, Germany
6 Klinikum der J.W. Goethe-Universität, Dr.
Senckenbergisches Institut für Neuroonkologie,
Frankfurt/Main, Germany
7 Medizinische Fakultät Mannheim, Zentrum für
Medizinische Forschung, Mannheim, Germany
8 Paracelsus Medical University, Department of Radiation
Oncology, Salzburg, Austria
9 University Hospital Frankfurt, Department of Radiation
Oncology, Frankfurt/Main, Germany
Purpose or Objective
Inter-individual variability in terms of treatment outcome
and benefit from standard of care treatment is a great
challenge in the multimodal therapy of glioblastoma
(GBM). In order to recognize patients with particularly
poor prognosis a priori and assigning them to alternative
treatment approaches, molecular signatures predicting
outcome with higher accuracy would be helpful. In our
study, we examined whether such a signature could be
defined on the basis of miRNA expression analyses.
Material and Methods
FFPE sections of resected tumours from 36 standard-of-
care treated GBM patients along with overall survival
follow-up data were collected retrospectively and
subjected to low-complexity signature identification from
miRNA microarray data. Based on the expression of the
signature miRNAs and cox-proportional hazard
coefficients, a risk score was calculated and used for
classification into higher- and lower-risk patients. The
identified signature was validated in a miRNA array data
set of a subset of the TCGA GBM cohort which was
matched for sex, age and treatment. In order to assess the
functional impact, genes putatively regulated by the
signature miRNAs were identified by correlation with
global transcriptome data, followed by pathway analysis.
Results
We identified a prognostic 4-miRNA signature that was
independent of MGMT promoter methylation status, age,
and sex. A risk score was assigned to each patient that
allowed defining two groups significantly differing in
prognosis (p-value: 0.0001, median survival: 10.6 months
and 15.1 months, hazard ratio = 3.8). The signature was
technically validated by qRT-PCR and independently
validated in an age- and sex-matched subset of standard-
of-care treated patients of the TCGA GBM cohort (n=58).
Pathway analysis suggested tumorigenesis-associated
processes such as immune response, extracellular matrix
organization, axon guidance, signalling by NGF, GPCR and
Wnt.
Conclusion
In the present study, we describe the identification and
independent validation of a 4-miRNA signature that allows
stratification of GBM patients into different prognostic
groups in combination with one defined threshold and set
of coefficients. This miRNA signature could be utilized as
diagnostic tool for the identification of GBM patients for
improved and/or alternative treatment approaches.
PO-0630 The role of mc4r gene polymorphisms in gbm
patients treated with concomitant radio-chemotherapy
M. Cantarella1, F. Pasqualetti1, A. Gonnelli1, P. Orlandi2,
D. Giuliani3, D. Delishaj1, S. Montrone1, G. Coraggio1, E.
Lombardo1, V. Simeon4, T. Di Desiderio2, A. Fioravanti2,
M. Fabrini 1, R. Danesi2, S. Guarini3, F. Paiar1, G. Bocci2
1Azienda Ospedaliero Universitaria Pisana, Radioterapia,
Pisa, Italy
2Azienda Ospedaliero Universitaria Pisana, Dipartimento
di Medicina Clinica e Sperimentale Sezione di
Farmacologia, Pisa, Italy
3Università di Modena e Reggio Emilia, Dipartimento di
Scienze Biomediche- Metaboliche e Neuroscienze Sezione
di Farmacologia e Medicina Molecolare, Modena e Reggio
Emilia, Italy
4Istituto di Cura a Carattere Scientifico Basilicata,
Laboratorio di ricerca preclinica e Traslazionale, Rionero
in Vulture, Italy
Purpose or Objective
Melanocortins are peptides with well-recognized anti-
inflammatory and neuroprotective activity. Melanocortin
receptor-4 (MC4R) is present in astrocytes and it is
expressed in the brain.. Given the association of MC4R
with antiinflammatory activity, induction of neural
stem/progenitor cell proliferation in brain hypoxia, and
prevention of astrocyte apoptosis, the aim of this study
was to evaluate the possible prognostic, predictive and
therapeutic role of the MC4R SNPs on GBM patients.
Material and Methods
Sixty-one patients with a proven diagnosis of GBM, ECOG
PS 0-2, age>18 years, and treated with radiotherapy and
temozolomide according to Stupp protocol were enrolled.
Genomic DNA was extracted and MC4R gene SNPs were
analyzed; the allelic discrimination was performed using
an ABI PRISM 7900 SDS (Applied Biosystems, Carlsbad, CA,
USA) and with validated TaqMan® SNP genotyping assays
(Applied Biosystems). Kaplan Meier curves were
performed for statistical association with genotypes. The
study has been approved by the Comitato Etico di Area
Vasta Nord Ovest prot. n. 17013.
Results
Fifty-six patients were clinically evaluated. The median
progression-free survival (PFS) and median overall
survival (OS) of these patients were 10.8 months and 23
months, respectively.. A relevant finding of our study was
the identification of a MC4R genotype that was
significantly associated with PFS: patients harbouring the
rs489693 AA genotype had a median PFS of 3 months