Victor Fritz1,2,3, Martin Schwartz1,4, Jens Kübler5, Jonas Habrich6, Simon Böke7, Daniela Thorwarth6, Konstantin Nikolaou5, and Fritz Schick1
1Department of Diagnostic and Interventional Radiology, University of Tuebingen, Section on Experimental Radiology, Tübingen, Germany, 2Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tuebingen, Tübingen, Germany, 3German Center for Diabetes Research (DZD), Neuherberg, Germany, 4Institute of Signal Processing and System Theory, University of Stuttgart, Stuttgart, Germany, 5Department of Diagnostic and Interventional Radiology, University of Tuebingen, University Hospital Tuebingen, Tübingen, Germany, 6Department of Radiation Oncology, University Hospital Tübingen, Section for Biomedical Physics, Tübingen, Germany, 7Department of Radiation Oncology, University Hospital Tübingen, University Hospital and Medical Faculty, Tübingen, Germany
Synopsis
Keywords: Cancer, Head & Neck/ENT
Motivation: Radiomic texture features are considered promising biomarkers for tumor’s response to therapy.
Goal(s): To identify texture features that can enhance predictive accuracy regarding tumor treatment outcomes.
Approach: The study included 13 patients with head and neck cancer undergoing radiation therapy, with MRI (T2w, DWI) conducted before treatment and during early-treatment phase. Image processing, tumor segmentation, and feature extraction are performed.
Results: Wilcoxon signed-rank tests with a Holm-Bonferroni correction reveals that Skewness in T2w-images exhibits significant changes during early treatment. This finding suggests that this feature may hold promise for predicting therapeutic responses, although larger studies are needed to confirm these results.
Impact: The study's preliminary findings suggest that Skewness in T2w images may have the potential to provide useful information for early response assessment in head and neck cancer patients undergoing radiation therapy, warranting further investigation to confirm its clinical significance.
Introduction
Great
efforts are being made to identify potential magnetic resonance imaging (MRI)
biomarkers that enable rapid and accurate prediction of tumor response to
therapy. In addition to inherent tissue properties such as apparent diffusion
coefficient (ADC) and relaxation times, radiomic texture features are
considered promising biomarkers for response monitoring and outcome prediction1-8. Texture features changing significantly between baseline (pre-treatment)
and the early treatment phase can potentially provide additional information
for an improved prediction of tumor response1,2.
The overall aim of this work was to
identify texture features that show significant changes in the early phase of
radiotherapy (RT) of head and neck cancer (HNC). For this, texture features were extracted on
segmented T2-weighted images and calculated ADC maps and compared at baseline
and in the early treatment phase.Methods
Patient cohort and image acquisition
The
study included 13 patients with locally advanced HNC who underwent radiation
therapy (RT). MRI was performed before treatment (baseline) and during the
second week of RT using a whole-body, 3.0T clinical system (MAGNETOM Vida,
Siemens Healthcare, Erlangen, Germany). T2w-images were acquired in the axial
plane with an inversion recovery prepared turbo spin echo sequence (STIR-TSE).
Diffusion-weighted MRI (DW-MRI) was performed using a spin-echo echo planar
imaging (SE-EPI) sequence with two b-values (DWIb50, DWIb800).
Acquisition parameters are listed in Table 1.
MR image preprocessing, segmentation and feature
extraction
The
image processing pipeline is schematically depicted in Figure 1. Tumor segmentation
was carried out by an
experienced radiologist (JK) using an open-source medical image computing
software (3D slicer9,https://www.slicer.org/). For each patient and each examination, the entire
tumor volume was manually segmented on T2w images. In addition, T1-weighted
dynamic contrast enhanced images were used as a reference for visual
co-registration. Due to image distortions in EPI-based diffusion-weighted
acquisitions, DW-MRI were registered on the distortion-free T2w image. Therefore, a rigid registration in the region
of the tumor segmentation according to Habrich et al.10 was performed using
elastix11,12. Due to the higher correspondence of the visible structures
between DWIb50 and T2w, DWIb50 was registered and the
transformation applied on DWIb800 accordingly. After image
registration, ADC maps were calculated using MATLAB® (The MathWorks,
Natick, MA, USA). Feature extraction was performed according to IBSI (Image
Biomarker Standardisation Initiative) guidelines using the open-source
PyRadiomics Python package13. A total number of 93 texture
features (First Order (18), Gray Level Cooccurrence Matrix-(GLCM) (24), Gray
Level Run Length Matrix-(GLRLM) (16), Gray Level Size Zone Matrix-(GLSZM) (16),
Neighbouring Gray Tone Difference Matrix-(NGTDM) (5), Gray Level Dependence
Matrix-(GLDM) (14)) were extracted from each segmented tumor in both normalized
T2w images and the computed ADC maps. The definitions and mathematical calculations
of the texture features can be found on the PyRadiomics documentation site
(https://pyradiomics.readthedocs.io/en/latest/features.html).
Statistical analysis
To
identify early treatment-induced changes in texture features, a two-sided
Wilcoxon signed-rank test with a significance level of α = 0.05 was used for three test cases: I) only T2w, II) only ADC and
III) T2w + ADC features. A Holm-Bonferroni correction was applied to compensate
for multiple testing. Since some features are volume-dependent14,15, these
radiomic features were normalized to the volume in order to determine
volume-independent changes. All statistical analyses were performed using
MATLAB®.Results
The
Holm-Bonferroni-corrected Wilcoxon signed-rank test revealed three texture
features on T2w that changed significantly in the early treatment phase:
Skewness(First Order),
Cluster shade(GLCM), and LALGLE(GLSZM) (Table 2,
Figure 2). However, LALGLE(GLSZM) proved to be volume-dependent and
showed no significant changes over the course of treatment after applying a
volume correction. For test case II (only ADC), there were only significant
changes regarding first order features mainly related to the known changes in
ADC values after RT16 (Figure 2). In a pooled analysis (test case III), only
the Skewness(First Order) in T2w and first order features in ADC are
still significant.Conclusion
Skewness(First Order)
extracted on T2w was identified as a texture feature that showed statistically
significant changes in the course of RT in head and neck cancer with and
without additional ADC features. Future studies with larger patient cohorts,
which is clearly a limitation of this preliminary study, will investigate
whether the skewness will still indicate significant changes and if it can
create synergies with established biomarkers (e.g. ADC values, relaxation
times) and thus provide useful information about the tumor's response to
therapy. Furthermore, an investigation of not yet included higher order
features might be also beneficial.
Acknowledgements
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