@article {80, title = {Data from: 4DCT imaging to assess radiomics feature stability: an investigation for thoracic cancers}, year = {2017}, publisher = {CancerData}, abstract = {

Background and Purpose
Quantitative tissue characteristics derived from medical images, also called radiomics, contain valuable prognostic information in several tumour-sites. The large number of features available increases the risk of overfitting. Typically test-retest CT-scans are used to reduce dimensionality and select robust features. However, these scans are not always available. We propose to use different phases of respiratory-correlated 4D CT-scans (4DCT) as alternative.\ 

Materials and Methods
In test-retest CT-scans of 26 non-small cell lung cancer (NSCLC) patients and 4DCT-scans (8 breathing phases) of 20 NSCLC and 20 oesophageal cancer patients, 1045 radiomics features of the primary tumours were calculated. A concordance correlation coefficient (CCC) \>0.85 was used to identify robust features. Correlation with prognostic value was tested using univariate cox regression in 120 oesophageal cancer patients.

Results
Features based on unfiltered images demonstrated greater robustness than wavelet-filtered features. In total 63/74 (85\%) unfiltered features and 268/299 (90\%) wavelet features stable in the 4D-lung dataset were also stable in the test-retest dataset. In oesophageal cancer 397/1045 (38\%) features were robust, of which 108 features were significantly associated with overall-survival.

Conclusion
4DCT-scans can be used as alternative to eliminate unstable radiomics features as first step in a feature selection procedure. Feature robustness is tumour-site specific and independent of prognostic value.


Venn chart visualizing the overlap of stable features with CCC\>0.85 in the test-retest lung (TR-lung), 4D-lung and 4D-oesophagus (4D-OES) dataset respectively.

}, keywords = {4D-CT, feature stability, lung cancer, oesophageal cancer, Radiomics, test-retest}, doi = {10.17195/candat.2017.05.1}, author = {Ruben T.H.M. Larue and Lien Van De Voorde and Janna E. van Timmeren and Ralph T.H. Leijenaar and Maaike Berbee and Meindert N. Sosef and Wendy M.J. Schreurs and Wouter van Elmpt and Philippe Lambin} } @article {77, title = {Data from: Survival prediction of non-small cell lung cancer patients using radiomics analyses of cone-beam CT images}, year = {2017}, abstract = {

Background and Purpose: In this study we investigated the interchangeability of planning CT and cone-beam CT (CBCT) extracted radiomic features. Furthermore, this study validates a previously\ described CT based prognostic radiomic signature for non-small cell lung cancer (NSCLC) patients using CBCT based features.

Material and Methods: One internal dataset of 132 and two external datasets of 62 and 94 stage I-IV NSCLC patients were included in this study. Interchangeability was assessed by performing a linear regression on CT and CBCT extracted features. A two-step correction was applied prior to model validation of a previously published radiomic signature.

Results: 13.3\% (149 out of 1119) of the radiomic features, including all features of the previously published radiomic signature, showed an R2 above 0.85 between intermodal imaging techniques. For the radiomic signature, Kaplan-Meier curves were significantly different between groups with high and low prognostic value for both modalities. Harrell{\textquoteright}s concordance index was 0.69 for CT and 0.66 for CBCT models for dataset 1.

Conclusions: The results show that a subset of radiomic features extracted from CT and CBCT images are interchangeable using simple linear regression. Moreover, a previously developed radiomics signature has prognostic value for overall survival in three CBCT cohorts, showing the potential of CBCT radiomics to be used as prognostic imaging biomarker.

Kaplan-Meier curves for pCT and CBCT. Kaplan-Meier curves are based on model predictions of the radiomic signature.

}, keywords = {computed tomography, cone-beam CT, non-small cell lung cancer, Radiomics, survival prediction}, doi = {10.17195/candat.2017.02.1}, author = {Janita van Timmeren and Ralph T.H. Leijenaar and Wouter van Elmpt and Bart Reymen and Cary Oberije and Ren{\'e} Monshouwer and Johan Bussink and Carsten Brink and Olfred Hansen and Philippe Lambin} } @article {72, title = {Data from: Nitroglycerin in non-small cell lung cancer: does it impact tumor hypoxia and tumor perfusion? A window-of-opportunity clinical trial.}, year = {2016}, abstract = {

Despite preclinical evidence that nitric oxide (NO) donors influence both tumor perfusion and hypoxia, in clinical trials nitroglycerin has not been shown to improve the treatment results of all patients with non-small cell lung cancer (NSCLC). Biomarkers are therefore needed to select patients for treatment with NO donors. In this window-of-opportunity study we demonstrate the effect of nitroglycerin on hypoxia in patients using repeated hypoxia PET-imaging: we observed a reduction of hypoxia - quantified by uptake of PET tracer HX4- of varying magnitude upon application of a nitroglycerin patch in approximately two thirds of patients with hypoxic loco-regional disease.

In a quarter of patients with baseline hypoxia, the tumor and nodes become normoxic after treatment with nitroglycerin. Furthermore, through dynamic contrast enhanced CT-scans (DCE-CT) we demonstrated that this effect on hypoxic tracer uptake is negatively correlated with tumor perfusion in hypoxic tumors.

Using in vitro experiments we show that the metabolism of 2-nitroimidazoles is not influenced by nitroglycerin itself and furthermore that nitroglycerin does not inhibit mitochondrial respiration at human achievable concentrations. Therefore, 2-nitroimidazole based imaging biomarkers can be used to evaluate the nitroglycerin treatment efficacy in an individual patient.\ 

The current results do support the hypothesis that hypoxia scans and/or DCE-CT scans could form a tool to select patients for a nitroglycerin patch adjuvant to anti-cancer treatment (radiotherapy, chemotherapy, targeted agents or immunotherapy) to increase drug uptake and/or to decrease hypoxia.

An animation summarizing our results is available at https://youtu.be/udJSBYaRv9w.

Figure 1. Uptake of HX4 before and after nitoglycerin administration

A. Images of a HX4 PET/CT scan before and after nitroglycerin administration of the same patient.
B. Evolution of high-uptake fraction (HF) of HX4 after application of nitroglycerin patch in baseline hypoxic lesions. Blue = decline \> CR of HX4 (17\%), grey = stable: change \< CR.

Note: dataset was updated 2017-11-24
}, doi = {10.17195/candat.2016.07.2}, author = {Bart Reymen and Marike W. van Gisbergen and Aniek J.G. Even and Catharina M.L. Zegers and Cary Oberije and Felix Mottaghy and Marco Das and Ala Yaromina and Wouter van Elmpt and Dirk De Ruysscher and Ludwig Dubois and Philippe Lambin} } @article {75, title = {Data from: Quantitative assessment of Zirconium-89 labeled cetuximab using PETCT imaging in patients with advanced head and neck cancer - a theragnostic approach}, year = {2016}, abstract = {

Biomarkers predicting treatment response to the monoclonal antibody cetuximab in locally advanced head and neck squamous cell carcinomas (LAHNSCC) are lacking. We hypothesize that tumor accessibility is an important factor in treatment success of the EGFR targeting drug. We quantified uptake of cetuximab labeled with Zirconium-89 (89Zr) using PET/CT imaging.
Seventeen patients with stage III-IV LAHNSCC received a loading dose unlabeled cetuximab, followed by 10 mg 54.5{\textpm}9.6 MBq 89Zr-cetuximab. PET/CT images were acquired either 3 and 6 or 4 and 7 days post-injection. 89Zr-cetuximab uptake was quantified using standardized uptake value (SUV) and tumor-to-background ratio (TBR), and correlated to EGFR immunohistochemistry. TBR was compared between scan days to determine optimal timing.
Uptake of 89Zr-cetuximab varied between patients (day 6-7: SUVpeak range 2.5-6.2). TBR increased significantly (49{\textpm}28\%, p\<0.01) between first (1.1{\textpm}0.3) and second scan (1.7{\textpm}0.6). Between groups with a low and high EGFR expression a significant difference in SUVmean (2.1 versus 3.0) and SUVpeak (3.2 versus 4.7) was found, however, not in TBR. Data is available at www.cancerdata.org.
In conclusion, 89Zr-cetuximab PET imaging shows large inter-patient variety in LAHNSCC and provides additional information over FDG-PET and EGFR expression. Validation of the predictive value is recommended with scans acquired 6-7 days post-injection.

Examples scans for four patients are provided. All patients received a planning PET/CT and two 89Zr-cetuximab scans. \ Patient P0037C0006I4475579 and P0037C0006I5879176 underwent 89Zr-cetuximab scans at 4 and 7 days post-injection; patient P0037C0006I6042760 and P0037C0006I8991415 at 3 and 6 days post-injection. All 89Zr-cetuximab PET scans are corrected for attenuation, scatter and 89Zr decay.

}, keywords = {cetuximab, EGFR, Immuno-PET, LAHNSCC, zirconium-89}, doi = {10.17195/candat.2016.11.1}, author = {Aniek Even and Olga Hamming-Vrieze and Wouter van Elmpt and V{\'e}ronique Winnepenninckx and Jolien Heukelom and Margot Tesselaar and Wouter Vogel and Ann Hoeben and Catharina M.L. Zegers and Danielle Vugts and Guus Van Dongen and Harry Bartelink and Felix Mottaghy and Frank Hoebers and Philippe Lambin} } Error | CancerData.org

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