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S320
ESTRO 36 2017
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partner site Tübingen, Tübingen, Germany
27
Faculty of Medicine and University Hospital Tübingen-
Eberhard Karls Universität Tübingen, Department of
Radiation Oncology, Tübingen, Germany
28
TU Dresden - Med. Faculty Carl Gustav Carus, Institute
of Pathology, Dresden, Germany
29
TU Dresden - Med. Faculty Carl Gustav Carus, Tumour-
and Normal Tissue Bank- University Cancer Centre UCC,
Dresden, Germany
30
TU Dresden - Med. Faculty Carl Gustav Carus, Medical
Systems Biology - University Cancer Centre UCC,
Dresden, Germany
Purpose or Objective
A gene signature predicting loco-regional control (LRC) of
locally advanced head and neck squamous cell carcinoma
(HNSCC) after postoperative radiochemotherapy (PORT-
C) will be evaluated using nanoString and RNA microarray
data. The prognostic power of the signature as well as the
correlation between both methods is evaluated to
underline the robustness of the proposed signature.
Material and Methods
Gene expression analyses were performed using
nanoString technology and the GeneChip® Human
Transcriptome Array 2.0 (Affymetrix) on a multicentre
retrospective patient cohort of 191 patients with HNSCC
who received postoperative radiochemotherapy. The
nanoString gene expression panel of 209 genes was
composed hypothesis-driven, 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.
A gene signature which optimally predicts LRC was
extracted from the nanoString gene expression data.
Different statistical methods for signature selection and
outcome prediction were compared. In parallel, this gene
signature was evaluated using gene expression data of the
GeneChip® Human Transcriptome Array analyses. The
prognostic performance of both methods, measured by the
concordance index (CI), was compared.
Results
The extracted nanoString gene signature contained genes
related to cellular proliferation, migration, invasion, and
tumour hypoxia. From the different statistical methods,
Cox regression performed best and was chosen for
outcome prediction. Internal 3-fold cross validation during
model building showed a CI≈0.7, indicating a good
performance of the model. Evaluating the signature using
the gene expression data generated with the GeneChip®
Human Transcriptome Array led to similar results. The
expression values of each gene within the signature were
significantly correlated between nanoString and RNA
microarray data with R>0.4.
Conclusion
We determined a gene signature for the prediction of LRC
in a cohort of 191 patients with locally advanced HNSCC
after postoperative radiochemotherapy based on
nanoString gene expression data. The signature showed a
good prognostic value and was validated by internal and
external validation. Using gene expression data from the
GeneChip® Human Transcriptome Array a similar
prognostic value was obtained, underlining the robustness
of the proposed signature.
PO-0620 Partial Laryngeal IMRT for T2N0 Glottic
Cancer: Impact of Image Guidance and Radiotherapy
Regimen
K. Rock
1
, S. Huang
1
, A. Tiong
1
, L. Lu
2
, W. Xu
2
, A. Bayley
1
,
S. Bratman
1
, J. Cho
1
, M. Giuliani
1
, A. Hope
1
, J. Kim
1
, J.
Ringash
1
, B. O'Sullivan
1
, J. Waldron
1
1
Princess Margaret Cancer Centre, Department of
Radiation Oncology, Toronto, Canada
2
Princess Margaret Cancer Centre, Department of
Biostatistics, Toronto, Canada
Purpose or Objective
Since 2006 we have used partial laryngeal IMRT due to the
ease of sparing the contralateral carotid and arytenoid
cartilage. Since then the protocol has undergone two
changes. Initially, the matching surrogate for image
guidance changed from cervical vertebrae bone (IGRT-
bone) to laryngeal soft tissue (IGRT-larynx). Secondly, the
IMRT dose/fractionation for T2N0 glottic cancer changed
from hypofractionation (RT-hypo) 60 Gy in 25 fractions in
5 wks (60 Gy/25f/5w) to moderate accelerated (RT-acc)
66-70 Gy/33-35f/5.5-6w. This study investigates the
impact of these two changes on local control (LC)
following partial laryngeal IMRT for T2N0 glottic cancer
patients.
Material and Methods
All clinical T2N0 glottic patients receiving partial laryngeal
IMRT from Jan 2006 to Dec 2013 were reviewed. GTV was
delineated based on endoscopic/radiological findings.
CTV1 was (GTV +0.3-0.5cm) to high dose and CTV2 (GTV
+1cm) to elective dose. PTV was CTV + 0.5cm expansion
axially but 1cm superior and inferiorly. LC, overall survival
(OS), and grade 3-4 late toxicity (LT) were compared
between IGRT-bone vs IGRT-larynx, and RT-hypo vs RT-
acc. Univariable analysis (UVA) was used to identify
potential factors for local failure (LF). Variables studied
included IGRT matching technique (IGRT-bone vs IGRT-
larynx), tumor volume and extension (supra- vs sub-
glottic), RT regimen, anterior commissure involvement
and smoking status. Since IGRT surrogate and RT regimen
were highly correlated, two separate multivariable
analysis (MVA) models were constructed.
Results
A total of 139 patients were identified. T2 category was
assigned as follows: supra- or sub-glottic extension (54%);
impaired vocal cord mobility (47%); or both (49%). Anterior
commissure involvement was present in 72% of patients.
IGRT-larynx and IGRT-bone were used in 92 (66%) and 47
(34%) patients, respectively. RT-hypo and RT-acc were
given to 71 (51%) and 68 (49%) patients, respectively.
Median follow-up was 5.03 yrs. A total of 28 local (IGRT-
bone:15/47, IGRT-larynx:13/92), 6 regional, 2 distant
failures were identified. Compared to IGRT-bone, IGRT-
larynx had higher 5 year LC (85% vs 68%, p=0.02) and OS
(87% vs 65%, p=0.007), but identical LT (7% vs 7%, p=0.73).
Higher LC was also observed for RT-acc vs RT-hypo (89% vs
70%, p=0.008). UVA revealed that IGRT-larynx (HR 0.42,
p=0.02), RT-acc (HR 0.33, p=0.01) were associated with
reduced risk for LF while current smoker did not impact
LC (p=0.49). MVA adjusted for GTV and smoking status
confirmed that IGRT-larynx reduced risk of LF vs IGRT-
bone (HR=0.40, 95% CI 1.2-5.3, p=0.02); RT-acc also
reduced risk of LF (HR 0.34, 0.15-0.79, p=0.012)
Conclusion
Moderate accelerated IMRT with laryngeal soft tissue
guidance for T2N0 glottic cancers results in high LC (>80%)
with minimal toxicity. The transition from bone vertebrae
to laryngeal soft tissue matching, together with
accelerated schedules and higher biological equivalent
dose is safe and potentially shows superior outcomes.
PO-0621 Validation of tumor delineation on HE stained
sections with cytokeratin staining as gold standard
H. Ligtenberg
1
, S. Willems
2
, E. Jager
1
, C. Terhaard
1
, C.
Raaijmakers
1
, M. Philippens
1
1
UMC Utrecht, Radiotherapy, Utrecht, The Netherlands
2
UMC Utrecht, Pathology, Utrecht, The Netherlands
Purpose or Objective
The extent of microscopic tumor growth determines the
clinical target volume (CTV) in head-and-neck tumors. In
imaging validation with histopathology, the CTV-margin
needed to include all microscopic tumor, can be
determined with microscopic investigation of
hematoxylin-eosin (HE) stained whole-mount slices. The