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O72. Autofluorescence imaging and biomarkers combined provide a predictive strategy in oral cavity malignancy
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80
Oral abstracts / Oral Oncology Supplement 3 (2009) 56–122
previous reports. The use of digital assessment of IHC expression provides objective and reproducible data which overcomes concerns over subjectivity of visual assessment, and hence improves interpretation of results. doi:10.1016/j.oos.2009.06.155
O71. Depth-sensitive optical spectroscopy for diagnosis of oral neoplasia R.A. Schwarz a,*, W. Gao a, C.R. Weber a, C. Kurachi b, R. Richards-Kortum a, A.M. Gillenwater c a
Rice University, United States University of Sao Paulo, Brazil c University of Texas, M.D. Anderson Cancer Center, United States b
Introduction: Depth-sensitive optical spectroscopy (DSOS) is a noninvasive method for measuring autofluorescence and diffuse reflectance spectra at different depths within tissue using a fiber optic point probe. DSOS has potential applications for diagnosis of oral neoplasia and may be employed alone or in combination with widefield imaging techniques. We evaluated the diagnostic potential of DSOS to distinguish neoplasia from normal oral mucosa in oral cancer patients and normal volunteers. Methods: Four hundred and twenty-four oral sites in 124 subjects (60 patients and 64 normal volunteers) were measured using the DSOS system. Algorithms were developed to identify the presence of neoplasia based on the measured spectra, and were tested using an independent validation subset. The sensitivity and specificity of DSOS were calculated using histopathology as the gold standard for sites in patients and expert clinical diagnosis as the gold standard for sites in volunteers. Results: Significant differences were observed between oral spectra from neoplastic and non-neoplastic sites, notably a reduction in blue-green autofluorescence intensity with disease progression. Differences were observed in spectra from non-keratinized and keratinized oral mucosa and different algorithms were developed to analyze these two classes of tissue. Spectral measurements targeting the deep epithelial/shallow stromal region were most diagnostically useful. Analysis of 310 non-keratinized sites resulted in an area under the receiver operating characteristic (ROC) curve of 0.96 in the training set and 0.93 in the validation set. Cross-validation analysis of 114 keratinized sites resulted in an area under the ROC curve of 0.76. Discussion: The ability of DSOS to target specific depth regions in tissue is helpful in spectroscopic diagnosis. For non-keratinized oral sites, the performance of DSOS approaches that of expert clinical diagnosis. DSOS is a potentially useful technique for noninvasive evaluation of oral lesions, particularly in community settings in which an expert observer is not available. doi:10.1016/j.oos.2009.06.156
O72. Autofluorescence imaging and biomarkers combined provide a predictive strategy in oral cavity malignancy E. Barker a,b, P. Reis b,*, G. Netchev b, R. Goswami b, B. Wilson b, J. Irish a a b
Princess Margaret Hospital, Toronto, Canada The Ontario Cancer Institute, The University of Toronto, Canada
Objective: To develop simultaneous fluorescence imaging and combined reflectance/fluorescence spectroscopy in the oral cavity.
In addition, to define molecular markers that can be used in combination with autofluorescent imaging analysis to predict ‘high-risk’ areas for underlying histological abnormality. Method: Twenty-two clinic patients underwent simultaneous fluorescence imaging and combined reflectance/fluorescence spectroscopy of their oral cavity. One to two ‘spots’ were collected for each patient and 100–300 spectra acquired per spot. Blood oxygenation and blood supply were derived from the reflectance spectra. Autofluorescence levels were determined within the green (450– 580 nm) band (S2). The autofluorescence was measured using a customized interference filter providing simultaneous leakage of reflected light in blue (400–450 nm) and red-NIR (690–750 nm) ranges (S1 and S3). Each patient was examined and recorded by both white-light and autofluorescent imaging using the Onco-LIFEÒ Endoscopic Light Source and Video Camera (Xillix Technologies Corp., Richmond, B.C. Canada). Discrepant areas of the oral mucosa (i.e. the mucosa appeared healthy with white-light, but had an abnormally low autofluorescence) were biopsied. In this pilot, immunohistochemistry was used to assess the status of p53 and EGFR. The autofluorescent and molecular marker results were compared against the histology. Results: In dysplastic or malignant lesions the autofluorescence images demonstrated a relatively low autofluorescence level. These results were consistent with the spectroscopy findings. The blood supply was increased in malignant lesions. Histology was classified into two categories: normal and abnormal (dysplasia and carcinoma). Using histology as the ‘gold standard’, the sensitivity and negative predictive values of EGFR, p53 and autofluorescence were 63%, 81%, 88% and 80%, 86%, 92% respectively. The best prediction model (C-statistics) is a combination of EGFR + p53+ autofluorescence (0.856). Conclusions: A combination of autofluorescent imaging and biomarker analyses will provide a robust predictive platform for assessment of mucosal oral malignancies. doi:10.1016/j.oos.2009.06.157
O73. Autofluorescence imaging for early detection of oral neoplasia A.M. Gillenwater a,*, D. Roblyer b, C. Kurachi c, V. Stepanek a, R. Richards-Kortum b a
University of Texas M.D. Anderson Cancer Center, United States Rice University, United States c University of São Paulo, Brazil b
Introduction: Imaging of tissue autofluorescence is a promising technique to improve detection of oral cancer and precancer in the oral cavity. Biochemical and structural changes in tissue associated with malignant progression may be revealed using autofluorescence imaging. The entire oral cavity can be screened in a non-invasive manner in real-time. We present results from a clinical study utilizing autofluorescence imaging of the oral cavity in human subjects. Methods: Fifty-six patients with confirmed or suspicious oral lesions and 11 normal volunteers were imaged using a fluorescence widefield clinical multispectral digital microscope (MDM). The MDM collects digital images using white light and fluorescence modalities from an approximately 5 cm field-of-view. Biopsies or surgical resection of imaged tissue were evaluated using histopathology and used as a gold standard for comparison. Measurements were split into separate training and validation sets. Regions-ofinterest in images corresponding to tissue areas of known pathology were quantitatively analyzed. Features extracted from these regions were used to train a simple classification algorithm. The
80
Oral abstracts / Oral Oncology Supplement 3 (2009) 56–122
previous reports. The use of digital assessment of IHC expression provides objective and reproducible data which overcomes concerns over subjectivity of visual assessment, and hence improves interpretation of results. doi:10.1016/j.oos.2009.06.155
O71. Depth-sensitive optical spectroscopy for diagnosis of oral neoplasia R.A. Schwarz a,*, W. Gao a, C.R. Weber a, C. Kurachi b, R. Richards-Kortum a, A.M. Gillenwater c a
Rice University, United States University of Sao Paulo, Brazil c University of Texas, M.D. Anderson Cancer Center, United States b
Introduction: Depth-sensitive optical spectroscopy (DSOS) is a noninvasive method for measuring autofluorescence and diffuse reflectance spectra at different depths within tissue using a fiber optic point probe. DSOS has potential applications for diagnosis of oral neoplasia and may be employed alone or in combination with widefield imaging techniques. We evaluated the diagnostic potential of DSOS to distinguish neoplasia from normal oral mucosa in oral cancer patients and normal volunteers. Methods: Four hundred and twenty-four oral sites in 124 subjects (60 patients and 64 normal volunteers) were measured using the DSOS system. Algorithms were developed to identify the presence of neoplasia based on the measured spectra, and were tested using an independent validation subset. The sensitivity and specificity of DSOS were calculated using histopathology as the gold standard for sites in patients and expert clinical diagnosis as the gold standard for sites in volunteers. Results: Significant differences were observed between oral spectra from neoplastic and non-neoplastic sites, notably a reduction in blue-green autofluorescence intensity with disease progression. Differences were observed in spectra from non-keratinized and keratinized oral mucosa and different algorithms were developed to analyze these two classes of tissue. Spectral measurements targeting the deep epithelial/shallow stromal region were most diagnostically useful. Analysis of 310 non-keratinized sites resulted in an area under the receiver operating characteristic (ROC) curve of 0.96 in the training set and 0.93 in the validation set. Cross-validation analysis of 114 keratinized sites resulted in an area under the ROC curve of 0.76. Discussion: The ability of DSOS to target specific depth regions in tissue is helpful in spectroscopic diagnosis. For non-keratinized oral sites, the performance of DSOS approaches that of expert clinical diagnosis. DSOS is a potentially useful technique for noninvasive evaluation of oral lesions, particularly in community settings in which an expert observer is not available. doi:10.1016/j.oos.2009.06.156
O72. Autofluorescence imaging and biomarkers combined provide a predictive strategy in oral cavity malignancy E. Barker a,b, P. Reis b,*, G. Netchev b, R. Goswami b, B. Wilson b, J. Irish a a b
Princess Margaret Hospital, Toronto, Canada The Ontario Cancer Institute, The University of Toronto, Canada
Objective: To develop simultaneous fluorescence imaging and combined reflectance/fluorescence spectroscopy in the oral cavity.
In addition, to define molecular markers that can be used in combination with autofluorescent imaging analysis to predict ‘high-risk’ areas for underlying histological abnormality. Method: Twenty-two clinic patients underwent simultaneous fluorescence imaging and combined reflectance/fluorescence spectroscopy of their oral cavity. One to two ‘spots’ were collected for each patient and 100–300 spectra acquired per spot. Blood oxygenation and blood supply were derived from the reflectance spectra. Autofluorescence levels were determined within the green (450– 580 nm) band (S2). The autofluorescence was measured using a customized interference filter providing simultaneous leakage of reflected light in blue (400–450 nm) and red-NIR (690–750 nm) ranges (S1 and S3). Each patient was examined and recorded by both white-light and autofluorescent imaging using the Onco-LIFEÒ Endoscopic Light Source and Video Camera (Xillix Technologies Corp., Richmond, B.C. Canada). Discrepant areas of the oral mucosa (i.e. the mucosa appeared healthy with white-light, but had an abnormally low autofluorescence) were biopsied. In this pilot, immunohistochemistry was used to assess the status of p53 and EGFR. The autofluorescent and molecular marker results were compared against the histology. Results: In dysplastic or malignant lesions the autofluorescence images demonstrated a relatively low autofluorescence level. These results were consistent with the spectroscopy findings. The blood supply was increased in malignant lesions. Histology was classified into two categories: normal and abnormal (dysplasia and carcinoma). Using histology as the ‘gold standard’, the sensitivity and negative predictive values of EGFR, p53 and autofluorescence were 63%, 81%, 88% and 80%, 86%, 92% respectively. The best prediction model (C-statistics) is a combination of EGFR + p53+ autofluorescence (0.856). Conclusions: A combination of autofluorescent imaging and biomarker analyses will provide a robust predictive platform for assessment of mucosal oral malignancies. doi:10.1016/j.oos.2009.06.157
O73. Autofluorescence imaging for early detection of oral neoplasia A.M. Gillenwater a,*, D. Roblyer b, C. Kurachi c, V. Stepanek a, R. Richards-Kortum b a
University of Texas M.D. Anderson Cancer Center, United States Rice University, United States c University of São Paulo, Brazil b
Introduction: Imaging of tissue autofluorescence is a promising technique to improve detection of oral cancer and precancer in the oral cavity. Biochemical and structural changes in tissue associated with malignant progression may be revealed using autofluorescence imaging. The entire oral cavity can be screened in a non-invasive manner in real-time. We present results from a clinical study utilizing autofluorescence imaging of the oral cavity in human subjects. Methods: Fifty-six patients with confirmed or suspicious oral lesions and 11 normal volunteers were imaged using a fluorescence widefield clinical multispectral digital microscope (MDM). The MDM collects digital images using white light and fluorescence modalities from an approximately 5 cm field-of-view. Biopsies or surgical resection of imaged tissue were evaluated using histopathology and used as a gold standard for comparison. Measurements were split into separate training and validation sets. Regions-ofinterest in images corresponding to tissue areas of known pathology were quantitatively analyzed. Features extracted from these regions were used to train a simple classification algorithm. The