A new tool to inform intra-operative decision making in skin cancer treatment: The non-invasive assessment of basal cell carcinoma of the skin using elastic scattering spectroscopy

Abstract

The aim of this study was to evaluate the findings of elastic scattering spectroscopy co-registered with histopathology in patients with basal cell carcinoma against normal and some common benign skin disorders.
Clinically suspicious head and neck skin lesions were included in this study. Those lesions with surrounding innocuous skin were interrogated by elastic scattering spectroscopy, co-registered biopsies were taken and examined histopathologically; the results were then compared using a variety of statistical techniques.
Our analysis showed obvious and consistent spectral differences between normal and pathological skin. Discriminating elastic spectral differences were consistently identified between basal cell carcinoma and other skin lesions of similar appearance.
This preliminary study shows that elastic scattering spectroscopy can distinguish between basal cell cancer, common benign conditions and variants of normal skin. Elastic scattering spectroscopy can also help determine the diagnosis between benign lesions with a high degree of accuracy suggesting that elastic scattering spectroscopy can add significant objectivity to dermatological diagnosis and management of even benign conditions.

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Compeng interests: none declared. Conict of interests: none declared.
All authors contributed to the concepon, design, and preparaon of the manuscript, as well as read and approved the nal manuscript.
All authors abide by the Associaon for Medical Ethics (AME) ethical rules of disclosure.
Original research study
   Upile T, Jerjes W, Johal O, Lew-Gor S, Mahil J, Sudhoff H. A new tool to inform intra-operative
   


Abstract
Introduction

-
  -
     
carcinoma against normal and some

Materials and methods
    
     
    -


    
-
-

Results
    
   -
 
Discriminating elastic spectral differ-
-

skin lesions of similar appearance.
Conclusion
    
elastic scattering spectroscopy can

-
ants of normal skin. Elastic scattering
    -
    
      -

   
A new tool to inform intra-operative decision making in skin cancer
treatment: the non-invasive assessment of basal cell carcinoma of
the skin using elastic scattering spectroscopy
T Upile32211
-
     
conditions.
Introduction
-
 -
     
 -

     -
    
-
        
     

    
    
-
     
    
-
-
   

    
   
    -
eas of cosmetic importance or near

 
important goals of disease removal

   -
    
    
      
proper treatment delivery and its ef-
-
    
     
    

 -

   
treatment.
    
-

and an improved prognosis for a pa-
     
    
    
-
  

   -
ment in ‘real-time’.
    

     
     
  

   
     -
  
    

       
related to its primary aetiology—

   -

neck    

       
     -
   -

     -
     
     
       
   
 -

is a good predictor of relative risk



1


2
 

3



   Upile T, Jerjes W, Johal O, Lew-Gor S, Mahil J, Sudhoff H. A new tool to inform intra-operative
   

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Compeng interests: none declared. Conict of interests: none declared.
All authors contributed to the concepon, design, and preparaon of the manuscript, as well as read and approved the nal manuscript.
All authors abide by the Associaon for Medical Ethics (AME) ethical rules of disclosure.
Original research study

-

     
   

   
      
    
    
   -
vanced disease.
     
-
     
     
    
    
    
    
    
      

   
in terms of errors of interpretation


    
weeks to complete and interpret).

    -
 
dependent.
     
 
    
    -


-
       -
     
-
 -
   



-

-
     
     
   


    -
   
   -
 -
    



    
     
  
consider elastic scattering spectros-
    
    
    -

-
 
-
-
 

     


  
 -
   

-
     
      
      -
   
      


    
   -
ganelles   
   -
   
-

 
    
-
    -
     
    
   
    

     
 -

     
non-invasively and in real-time.
Materials and methods
     
 -
     
    
     -

     
-
      -
      


   
      -
tailed2     

     
     
of concern. If excision was clinically
-

-
  
   


      
   
      
  
   
    

  
   
   
   
     
      -

-
    
     
     
    

    

Page 3 of 8
Compeng interests: none declared. Conict of interests: none declared.
All authors contributed to the concepon, design, and preparaon of the manuscript, as well as read and approved the nal manuscript.
All authors abide by the Associaon for Medical Ethics (AME) ethical rules of disclosure.
   Upile T, Jerjes W, Johal O, Lew-Gor S, Mahil J, Sudhoff H. A new tool to inform intra-operative
   

Original research study

   
  

 
 -
    

-
    
     

24.
Results
    
    
±


 -

    
 
    -


    
lesions for comparative analysis. No
    -

-


    
   
    -
    
-

     
-
     
     

in a cosmetically sensitive manner.

   

Statistical approach for model
generation and model validation
    
     


  2   
     -
 
-
    -
    

     

   -
    
    
   

discriminate analysis (LDA) strate-
     
-
       
   
-
   

   

    
    
-
-

Table 1 The 4 most common
pathologies of the paent populaon
studied
Diagnosis %
BCC 28.8
Intra-dermal naevus 21.9
Fibro-epithelial polyp 13.7
Seborrhoeic keratosis 9.6
Other benign lesions 26
Table 2 The number of pathological
sites interrogated and number of
site specic spectra obtained
Number
of sites
Number
of spectra
BCC 59 570
Intra-dermal
naevus
31 633
Fibro-epithelial
polyp
23 502
Benign
seborrhoeic
keratosis
12 269
Normal skin 125 551
400
−2
500 600
Wavelength
700 800
−1
0
Intensity
1
2
Figure 1: A representative elastic
     
   
   
-


−5
0.0
0 5
Score
10
0.1
0.2
0.3
Frequency
0.4
0.5
400
−2
−1
0
Intensity
1
2
400 600
Wavelength
700 800
Figure 2:    
   -
   

    
-
     

 
plot2     
   
   
    -
sis (orange) spectra.

   Upile T, Jerjes W, Johal O, Lew-Gor S, Mahil J, Sudhoff H. A new tool to inform intra-operative
   

Page 4 of 8
Compeng interests: none declared. Conict of interests: none declared.
All authors contributed to the concepon, design, and preparaon of the manuscript, as well as read and approved the nal manuscript.
All authors abide by the Associaon for Medical Ethics (AME) ethical rules of disclosure.
Original research study


   
     
 
     -
    

 
-
     
   
   -
     
     

    -

    
-
     
 
      
   
   

    
   -

     
    
      
  
 
Table 3 Analysis results and ability of the elasc spectroscopy technique to discriminate between normal, benign and
malignant lesions. Also shown is the similar discriminang ability of the technique when comparing readings taken from
the periphery of a BCC and the centre of the BCC
Sensivity Specicity Accuracy
Per spectra Per site Per spectra Per site Per spectra Per site
BCC vs intra-dermal naevus 0.8789474 0.9859155 0.9787928 0.8846154 0.9306847 0.9587629
BCC vs bro-epithelial polyp 0.8385965 0.9577465 0.8884462 0.7826087 0.8619403 0.9148936
BCC vs benign seborrhoeic keratosis 0.9543860 1 0.9665428 0.9166667 0.9582837 0.9879518
BCC vs normal 0.8842105 0.9436620 0.7422868 0.4324324 0.8144514 0.6827586
BCC periphery vs BCC centre 0.115880 0.3750000 0.6720257 0.3939394 0.4319853 0.3846154
Intra-dermal naevus vs bro-epithelial polyp 0.8036466 1.0000000 0.8286853 0.6521739 0.8139918 0.8490566
Intra-dermal naevus vs benign seborrhoeic
keratosis
0.6579926 0.7500000 0.9929874 0.8666667 0.9012220 0.8333333
Fibro-epithelial polyp vs benign seborrhoeic
keratosis
0.8996283 0.9166667 0.9581673 0.7391304 0.9377432 0.8000000
0.0 0.2 0.4
0.0
0.6 0.8
1-specificity
1.0
0.2
0.4
0.6
Sensivity
0.8
1.0
Figure 3:     
   
   -
    
    

400
−2
500 600
Wavelength
700 800
−1
0
Intensity
1
2
Figure 4: A representative elastic
     

     
   

−5
0.0
0 5
Score
10
0.2
0.4
0.8
Frequency
0.6
1.0
1.2
400
−2
−1
0
Intensity
1
2
400 600
Wavelength
700 800
Figure 5:    
   -
   
     
    -
    
  -
     
   2 

   




Compeng interests: none declared. Conict of interests: none declared.
All authors contributed to the concepon, design, and preparaon of the manuscript, as well as read and approved the nal manuscript.
All authors abide by the Associaon for Medical Ethics (AME) ethical rules of disclosure.
   Upile T, Jerjes W, Johal O, Lew-Gor S, Mahil J, Sudhoff H. A new tool to inform intra-operative
   

Original research study

-

    


-
      


     
 
     
    
   
operative cancer resection and
 -
    
     
    
since clones of differing aggressivity

   
 
-

Discussion
    
  -
    -
    
 
     -

    -
    -
      

    
 
-
    
     -
   
   
 -
terpreted as an indicative of cancer.
 
     -
      
      -
     
0.0 0.2 0.4
0.0
0.6 0.8
1-specificity
1.0
0.2
0.4
0.6
Sensivity
0.8
1.0
Figure 6:     
     
    
    

400
−2
500 600
Wavelength
700 800
−1
0
Intensity
1
2
Figure 7: A representative elastic
     
     
     
 
    
-


−5
0.0
0 5
Score
10
0.1
0.3
Frequency
0.2
0.4
0.5
400
−2
−1
0
Intensity
1
2
400 600
Wavelength
700 800
Figure 8:    
   -
     
     
    
     


2

    
    
  
 

   
-


Figure 9:
   


trade-off of sensitivity against specif-
-

    




     
     

-
   
   -
      

   

0.0 0.2 0.4
0.0
0.6 0.8
1-specificity
1.0
0.2
0.4
0.6
Sensivity
0.8
1.0

   Upile T, Jerjes W, Johal O, Lew-Gor S, Mahil J, Sudhoff H. A new tool to inform intra-operative
   


Compeng interests: none declared. Conict of interests: none declared.
All authors contributed to the concepon, design, and preparaon of the manuscript, as well as read and approved the nal manuscript.
All authors abide by the Associaon for Medical Ethics (AME) ethical rules of disclosure.
Original research study


-
     
   
       
lesions in a primary care setting2. It is


     -
     
    
-
      

 -


-


  
resection in primary care settings
    
-

    -
     -


-

patient care.
Challenges
     
  

    


     
-
  
-
-

2
-
     


-

400 500 600
−2
700
Wavelength
800
−1
0
1
Intensity
2
Figure 10:   -
 
    -
   
   
   
    
 -
-
nign lesions and normal.
Table 4 BCC vs normal skin results
Comparison of the histological diagnosis and ESS in the diagnosis of the skin pathology group
Test: ESS
diagnosis
Disease: BCC histological diagnosis (Gold standard)
Sites BCC Normal Total (n)
BCC (59) True posive (TP) 397 False posive (FP) 29 All with posive test = (TP + FP) 426
Normal (125) False negave (FN) 113 True negave (TN) 118 All with negave test = (FN + TN) 231
Total (n) All with disease 510 All without disease 147 All = (TP + FP + FN + TN) 657
Sensivity = TP/(TP + FN) 77.8%
Specicity = TN/(TN + FP) 80.3%
Pre-test probability = (TP + FN)/(TP + FP + FN + TN) 64.8%
Posive predicve value = TP/(TP + FP) 93.2%
Negave predicve value = TN/(FN + TN) 51.1%
0.0 0.2 0.4
0.0
0.6 0.8
1-specificity
1.0
0.2
0.4
0.6
Sensivity
0.8
1.0
Figure 11:  
    
    
   -
  

 -

     
    
    
    
    -
 
  
    



Compeng interests: none declared. Conict of interests: none declared.
All authors contributed to the concepon, design, and preparaon of the manuscript, as well as read and approved the nal manuscript.
All authors abide by the Associaon for Medical Ethics (AME) ethical rules of disclosure.
   Upile T, Jerjes W, Johal O, Lew-Gor S, Mahil J, Sudhoff H. A new tool to inform intra-operative
   

Original research study

      
-
cal intranodal metastasis in oral cancer
   

      
     
     
    


      

   -
  
    

      
-
cal intranodal metastasis in oral cancer
   

   -

    

      
     
  
   
     -
     

      

-
     
    


    
    -
gramme for oral cancer and precancer
     

      
      
    
      
    

 


      
     
    -
   
   
    
       
    
     -
      
   
      -
     
-
     
conditions.
Abbreviations list

   
    
   
   
  
-

Acknowledgement
     

Declaration

-
      
 
     

References

     
      
   

   
     -

   

        
       
   


      
-
     
-
    

  -
tion alone2 -
      
    



    -
  
 -
    
     

    


    

Conclusion
    
    
-

-
      
  
    
 -
   
     

     
    -
ness and non-operator dependence.
    
     -
  -
    
improve management and prognosis.
 -
-
     
-
-

     
-
    
     

     
-
     

   Upile T, Jerjes W, Johal O, Lew-Gor S, Mahil J, Sudhoff H. A new tool to inform intra-operative
   

Page 8 of 8
Compeng interests: none declared. Conict of interests: none declared.
All authors contributed to the concepon, design, and preparaon of the manuscript, as well as read and approved the nal manuscript.
All authors abide by the Associaon for Medical Ethics (AME) ethical rules of disclosure.
Original research study

     -
    -


-
    -
gramme for oral cancer and precancer
     

      
       
Elastic scattering spectroscopy for
     
   

   
    
044022.
    
diagnosis of non-melanoma skin cancer
     
   -


      
   
      

     

       
   

       
   

    
    

        
Real-time Raman spectroscopy for non-
invasive skin cancer detection—prelimi-



     
     
-
  
     

    
     
      