Kaissis, G.* ; Ziegelmayer, S.* ; Lohöfer, F.* ; Steiger, K.* ; Algül, H.* ; Muckenhuber, A.* ; Yen, H.Y.* ; Rummeny, E.* ; Friess, H.* ; Schmid, R.* ; Weichert, W.* ; Siveke, J.T.* ; Braren, R.*
    
 
    
        
A machine learning algorithm predicts molecular subtypes in pancreatic ductal adenocarcinoma with differential response to gemcitabine-based versus FOLFIRINOX chemotherapy.
    
    
        
    
    
        
        PLoS ONE 14:e0218642 (2019)
    
    
    
		
		
			
				PURPOSE: Development of a supervised machine-learning model capable of predicting clinically relevant molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) from diffusion-weighted-imaging-derived radiomic features. METHODS: The retrospective observational study assessed 55 surgical PDAC patients. Molecular subtypes were defined by immunohistochemical staining of KRT81. Tumors were manually segmented and 1606 radiomic features were extracted with PyRadiomics. A gradient-boosted-tree algorithm was trained on 70% of the patients (N = 28) and tested on 30% (N = 17) to predict KRT81+ vs. KRT81- tumor subtypes. A gradient-boosted survival regression model was fit to the disease-free and overall survival data. Chemotherapy response and survival were assessed stratified by subtype and radiomic signature. Radiomic feature importance was ranked. RESULTS: The mean±STDEV sensitivity, specificity and ROC-AUC were 0.90±0.07, 0.92±0.11, and 0.93±0.07, respectively. The mean±STDEV concordance indices between the disease-free and overall survival predicted by the model based on the radiomic parameters and actual patient survival were 0.76±0.05 and 0.71±0.06, respectively. Patients with a KRT81+ subtype experienced significantly diminished median overall survival compared to KRT81- patients (7.0 vs. 22.6 months, HR 4.03, log-rank-test P = <0.001) and a significantly improved response to gemcitabine-based chemotherapy over FOLFIRINOX (10.14 vs. 3.8 months median overall survival, HR 2.33, P = 0.037) compared to KRT81- patients, who responded significantly better to FOLFIRINOX over gemcitabine-based treatment (30.8 vs. 13.4 months median overall survival, HR 2.41, P = 0.027). Entropy was ranked as the most important radiomic feature. CONCLUSIONS: The machine-learning based analysis of radiomic features enables the prediction of subtypes of PDAC, which are highly relevant for disease-free and overall patient survival and response to chemotherapy.
			
			
				
			
		 
		
			
				
					
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        Publikationstyp
        Artikel: Journalartikel
    
 
    
        Dokumenttyp
        Wissenschaftlicher Artikel
    
 
    
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        englisch
    
 
    
        Veröffentlichungsjahr
        2019
    
 
    
        Prepublished im Jahr 
        
    
 
    
        HGF-Berichtsjahr
        2019
    
 
    
    
        ISSN (print) / ISBN
        1932-6203
    
 
    
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	    Band: 14,  
	    Heft: 10,  
	    Seiten: ,  
	    Artikelnummer: e0218642 
	    Supplement: ,  
	
    
 
  
        
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            Verlag
            Public Library of Science (PLoS)
        
 
        
            Verlagsort
            Lawrence, Kan.
        
 
	
        
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        Peer reviewed
    
 
     
    
        POF Topic(s)
        30205 - Bioengineering and Digital Health
    
 
    
        Forschungsfeld(er)
        Enabling and Novel Technologies
    
 
    
        PSP-Element(e)
        G-530014-001
    
 
    
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        Erfassungsdatum
        2022-09-13