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ESTRO 35 2016 S279
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2
German Cancer Research Center DKFZ, Heidelberg and
German Cancer Consortium DKTK partner site Dresden,
Dresden, Germany
3
Helmholtz-Zentrum Dresden – Rossendorf, Institute of
Radiooncology, Dresden, Germany
5
Faculty of Medicine and University Hospital Carl Gustav
Carus- Technische Universität Dresden, Department of
Radiation Oncology, Dresden, Germany
6
Faculty of Medicine and University Hospital Carl Gustav
Carus- Technische Universität Dresden, Department of
Otorhinolaryngology, Dresden, Germany
7
Faculty of Medicine and University Hospital Carl Gustav
Carus- Technische Universität Dresden, Department of Oral
and Maxillofacial Surgery, Dresden, Germany
8
German Cancer Research Center DKFZ, Heidelberg and
German Cancer Consortium DKTK partner site Berlin, Berlin,
Germany
9
Charité University Hospital, Department of Radiooncology
and Radiotherapy, Berlin, Germany
10
German Cancer Research Center DKFZ, Heidelberg and
German Cancer Consortium DKTK partner site Essen, Essen,
Germany
11
Medical Faculty- University of Duisburg-Essen, Department
of Radiotherapy, Essen, Germany
12
Goethe-University Frankfurt, Department of Radiotherapy
and Oncology, Frankfurt am Main, Germany
13
German Cancer Research Center DKFZ, Heidelberg and
German Cancer Consortium DKTK partner site Frankfurt,
Frankfurt am Main, Germany
14
Department of Radiotherapy and Oncology, Goethe-
University Frankfurt, Frankfurt am Main, Germany
15
German Cancer Research Center DKFZ, Heidelberg and
German Cancer Consortium DKTK partner site Freiburg,
Freiburg, Germany
16
University of Freiburg- Germany, Department of Radiation
Oncology- Clinical Study Section, Freiburg, Germany
17
University of Freiburg, Department of Radiation Oncology,
Freiburg, Germany
18
German Cancer Research Center DKFZ, Heidelberg and
German Cancer Consortium DKTK partner site Heidelberg,
Heidelberg, Germany
19
University of Heidelberg Medical School and German Cancer
Research Center DKFZ, Translational Radiation Oncology,
Heidelberg, Germany
20
University of Heidelberg Medical School and German Cancer
Research Center DKFZ, National Center for Tumor Diseases
NCT, Heidelberg, Germany
21
University of Heidelberg Medical School- Heidelberg Ion
Therapy Center HIT, Department of Radiation Oncology,
Heidelberg, Germany
22
University of Heidelberg Medical School and German Cancer
Research Center DKFZ, Heidelberg Institute of Radiation
Oncology HIRO- National Center for Radiation Research in
Oncology NCRO, Heidelberg, Germany
23
University of Heidelberg Medical School and German Cancer
Research Center DKFZ, Clinical Cooperation Unit Radiation
Oncology, Heidelberg, Germany
24
German Cancer Research Center DKFZ, Heidelberg and
German Cancer Consortium DKTK partner site Munich,
München, Germany
25
Ludwig-Maximilians-Universität,
Department
of
Radiotherapy and Radiation Oncology, München, Germany
26
Technische Universität München, Department of Radiation
Oncology, München, Germany
27
Department of Radiation Oncology, Technische Universität
München, München, Germany
28
German Cancer Research Center DKFZ, Heidelberg and
German Cancer Consortium DKTK partner site Tübingen,
Tübingen, Germany
29
Faculty of Medicine and University Hospital Tübingen-
Eberhard Karls Universität Tübingen, Department of
Radiation Oncology, Tübingen, Germany
30
University Hospital Carl Gustav Carus- Technische
Universität Dresden, Tumour- and Normal Tissue Bank-
University Cancer Centre UCC, Dresden, Germany
31
Faculty of Medicine and University Hospital Carl Gustav
Carus- Technische Universität Dresden, Institute of
Pathology, Dresden, Germany
32
University Hospital Carl Gustav Carus- Technische
Universität Dresden, University Cancer Centre UCC- Medical
Systems Biology, Dresden, Germany
Purpose or Objective:
To determine gene signatures which
predict loco-regional control (LRC) and the secondary
endpoints overall survival (OS) and freedom of distant
metastases (FDM) of locally advanced head and neck
squamous cell carcinoma (HNSCC) after postoperative
radiochemotherapy.
Material and Methods:
A gene expression panel of 216 genes
was composed including genes which are involved in
proliferation, invasion and metastasis as well as in
radio(chemo)resistance associated with tumour hypoxia,
cancer stem cell markers, cisplatin-resistance and DNA
repair. Gene expression analysis was performed using
NanoString technology on a multicentre retrospective patient
cohort of 196 patients with HNSCC who received
postoperative radiochemotherapy. Gene signatures with a
minimal number of contributing genes were extracted, which
optimally predict for LRC and the secondary endpoints OS and
FDM. For the construction of these minimal signatures,
different statistical methods were compared, including Cox
regression with forward variable selection, boosting methods
and random forests. To assess the performance of the
different gene signatures and statistical methods the
concordance index (CI) was evaluated using 3-fold internal
cross validation.
Results:
The resulting gene signatures mostly contained
genes related to cellular proliferation, migration, invasion,
and tumour hypoxia. For all endpoints and statistical methods
a cross-validated CI>0.7 could be obtained, indicating a good
performance of the models. Using the linear predictor
as a risk variable allowed for splitting the patient cohort into
groups of good and bad prognosis. The figure exemplarily
shows Kaplan-Meier curves of the total patient cohort split by
the median risk variable of the gene signatures determined
by Cox regression with forward variable selection for all
endpoints. The difference between the survival curves is
highly significant (p<0.001).