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S868

ESTRO 36

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Conclusion

Varying the RBE depending on end-point may strongly

influence results when estimating carcinogenic risks from

C-ion therapy and should be included in modelling risk of

radiation-induced SC from C-ion therapy.

EP-1608 Deriving HPV status from standard CT imaging:

a radiomic approach with independent validation

R. Leijenaar

1

, M. Nesteruk

2

, G. Feliciani

1

, F. Hoebers

1

, J.

Van Timmeren

1

, W. Van Elmpt

1

, S. Walsh

1

, A. Jochems

1

,

S. Huang

3

, B. Chan

3

, J. Waldron

3

, B. O'Sullivan

3

, D.

Rietveld

4

, C. Leemans

5

, O. Riesterer

2

, K. Ikenberg

6

, P.

Lambin

1

1

MAASTRO Clinic, Department of Radiation Oncology-

GROW- School for Oncology and Developmental Biology-

Maastricht University Medical Centre, Maastricht, The

Netherlands

2

University Hospital Zurich and University of Zurich,

Department of Radiation Oncology, Zurich, Switzerland

3

Princess Margaret Cancer Center, Department of

Radiation Oncology- University of Toronto, Toronto,

Canada

4

VU University Medical Center, Department of Radiation

Oncology, Amsterdam, The Netherlands

5

VU University Medical Center, Department of

Otolaryngology/Head and Neck Surgery, Amsterdam, The

Netherlands

6

University Hospital Zurich and University of Zurich,

Department of Pathology and Molecular Pathology,

Zurich, Switzerland

Purpose or Objective

Oropharyngeal squamous cell carcinoma (OPSCC) is one of

the fastest growing disease sites of head and neck cancers.

HPV positive cancers have been shown to have better

tumor control with radiotherapy and increased survival,

which makes them interesting for de-escalation protocols.

HPV is routinely tested using in situ hybridization for viral

DNA, or immunohistochemistry for p16. However, an

established, non-invasive, imaging biomarker of HPV

status currently does not exist. Radiomics–the high-

throughput extraction of large amounts of quantitative

features from medical images–has already been shown to

be of prognostic value for head and neck cancer. In this

study we evaluate the use of a Radiomic approach to

identify the HPV status of OPSCC patients.

Material and Methods

Three independent cohorts, with a total of 793 OPSCC

patients were collected: C1 (N=543), C2 (N=159) and C3

(N=100). HPV status was determined by p16 and available

for 686 patients. Patients underwent pre-treatment CT

imaging and the tumor volume was manually delineated

for treatment planning purposes. Images were visually

assessed for the presence of CT artifacts (e.g. streak

artifacts due to dental fillings) within the GTV, in which

case they were excluded from further analysis. In total,

1378 Radiomic features were extracted, comprising: a)

first-order statistics, b) shape, and c) (multiscale) texture

(Laplacian of Gaussian and Wavelet). The model was

learned on the C1 cohort and validated on the remaining

cohorts. The Radiomic feature space was first reduced by

selecting cluster medoids after hierarchical cluster

analysis using correlation (ρ>0.9) as a distance measure.

Multivariable logistic regression was performed using least

absolute shrinkage and selection operator (LASSO) model

selection (200 times 10-fold cross-validated). The area

under the receiver operator curve was used to assess out-

of-sample model performance in predicting HPV status.

Results

Out of the patients with known HPV scoring, we identified

337 (49%) patients without visible CT artifacts: C1

(N=206), C2 (N=88), C3 (N=43), of which 132, 20, and 18

were HPV positive, respectively. The modeling process

resulted in a multivariable prediction model, with an AUC

of 0.85. External validation in the C2 and C3 cohorts

showed an AUC of 0.6 and 0.72, respectively. The receiver

operator curves for training and validation are shown in

Figure

1.