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Computerized Image Analysis of Tumor Cell Nuclear Morphology Can Improve Patient Selection for Clinical Trials in Localized Clear Cell Renal Cell Carcinoma
BACKGROUND: Clinicopathological scores are used to predict the likelihood of recurrence-free survival for patients with clear cell renal cell carcinoma (ccRCC) after surgery. These are fallible, particularly in the middle range. This inevitably means that a significant proportion of ccRCC patients w...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer - Medknow
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737492/ https://www.ncbi.nlm.nih.gov/pubmed/33343995 http://dx.doi.org/10.4103/jpi.jpi_13_20 |
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author | Um, In Hwa Scott-Hayward, Lindesay Mackenzie, Monique Tan, Puay Hoon Kanesvaran, Ravindran Choudhury, Yukti Caie, Peter D. Tan, Min-Han O'Donnell, Marie Leung, Steve Stewart, Grant D. Harrison, David J. |
author_facet | Um, In Hwa Scott-Hayward, Lindesay Mackenzie, Monique Tan, Puay Hoon Kanesvaran, Ravindran Choudhury, Yukti Caie, Peter D. Tan, Min-Han O'Donnell, Marie Leung, Steve Stewart, Grant D. Harrison, David J. |
author_sort | Um, In Hwa |
collection | PubMed |
description | BACKGROUND: Clinicopathological scores are used to predict the likelihood of recurrence-free survival for patients with clear cell renal cell carcinoma (ccRCC) after surgery. These are fallible, particularly in the middle range. This inevitably means that a significant proportion of ccRCC patients who will not develop recurrent disease enroll into clinical trials. As an exemplar of using digital pathology, we sought to improve the predictive power of “recurrence free” designation in localized ccRCC patients, by precise measurement of ccRCC nuclear morphological features using computational image analysis, thereby replacing manual nuclear grade assessment. MATERIALS AND METHODS: TNM 8 UICC pathological stage pT1-pT3 ccRCC cases were recruited in Scotland and in Singapore. A Leibovich score (LS) was calculated. Definiens Tissue studio® (Definiens GmbH, Munich) image analysis platform was used to measure tumor nuclear morphological features in digitized hematoxylin and eosin (H&E) images. RESULTS: Replacing human-defined nuclear grade with computer-defined mean perimeter generated a modified Leibovich algorithm, improved overall specificity 0.86 from 0.76 in the training cohort. The greatest increase in specificity was seen in LS 5 and 6, which went from 0 to 0.57 and 0.40, respectively. The modified Leibovich algorithm increased the specificity from 0.84 to 0.94 in the validation cohort. CONCLUSIONS: CcRCC nuclear mean perimeter, measured by computational image analysis, together with tumor stage and size, node status and necrosis improved the accuracy of predicting recurrence-free in the localized ccRCC patients. This finding was validated in an ethnically different Singaporean cohort, despite the different H and E staining protocol and scanner used. This may be a useful patient selection tool for recruitment to multicenter studies, preventing some patients from receiving unnecessary additional treatment while reducing the number of patients required to achieve adequate power within neoadjuvant and adjuvant clinical studies. |
format | Online Article Text |
id | pubmed-7737492 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Wolters Kluwer - Medknow |
record_format | MEDLINE/PubMed |
spelling | pubmed-77374922020-12-18 Computerized Image Analysis of Tumor Cell Nuclear Morphology Can Improve Patient Selection for Clinical Trials in Localized Clear Cell Renal Cell Carcinoma Um, In Hwa Scott-Hayward, Lindesay Mackenzie, Monique Tan, Puay Hoon Kanesvaran, Ravindran Choudhury, Yukti Caie, Peter D. Tan, Min-Han O'Donnell, Marie Leung, Steve Stewart, Grant D. Harrison, David J. J Pathol Inform Research Article BACKGROUND: Clinicopathological scores are used to predict the likelihood of recurrence-free survival for patients with clear cell renal cell carcinoma (ccRCC) after surgery. These are fallible, particularly in the middle range. This inevitably means that a significant proportion of ccRCC patients who will not develop recurrent disease enroll into clinical trials. As an exemplar of using digital pathology, we sought to improve the predictive power of “recurrence free” designation in localized ccRCC patients, by precise measurement of ccRCC nuclear morphological features using computational image analysis, thereby replacing manual nuclear grade assessment. MATERIALS AND METHODS: TNM 8 UICC pathological stage pT1-pT3 ccRCC cases were recruited in Scotland and in Singapore. A Leibovich score (LS) was calculated. Definiens Tissue studio® (Definiens GmbH, Munich) image analysis platform was used to measure tumor nuclear morphological features in digitized hematoxylin and eosin (H&E) images. RESULTS: Replacing human-defined nuclear grade with computer-defined mean perimeter generated a modified Leibovich algorithm, improved overall specificity 0.86 from 0.76 in the training cohort. The greatest increase in specificity was seen in LS 5 and 6, which went from 0 to 0.57 and 0.40, respectively. The modified Leibovich algorithm increased the specificity from 0.84 to 0.94 in the validation cohort. CONCLUSIONS: CcRCC nuclear mean perimeter, measured by computational image analysis, together with tumor stage and size, node status and necrosis improved the accuracy of predicting recurrence-free in the localized ccRCC patients. This finding was validated in an ethnically different Singaporean cohort, despite the different H and E staining protocol and scanner used. This may be a useful patient selection tool for recruitment to multicenter studies, preventing some patients from receiving unnecessary additional treatment while reducing the number of patients required to achieve adequate power within neoadjuvant and adjuvant clinical studies. Wolters Kluwer - Medknow 2020-11-06 /pmc/articles/PMC7737492/ /pubmed/33343995 http://dx.doi.org/10.4103/jpi.jpi_13_20 Text en Copyright: © 2020 Journal of Pathology Informatics http://creativecommons.org/licenses/by-nc-sa/4.0 This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. |
spellingShingle | Research Article Um, In Hwa Scott-Hayward, Lindesay Mackenzie, Monique Tan, Puay Hoon Kanesvaran, Ravindran Choudhury, Yukti Caie, Peter D. Tan, Min-Han O'Donnell, Marie Leung, Steve Stewart, Grant D. Harrison, David J. Computerized Image Analysis of Tumor Cell Nuclear Morphology Can Improve Patient Selection for Clinical Trials in Localized Clear Cell Renal Cell Carcinoma |
title | Computerized Image Analysis of Tumor Cell Nuclear Morphology Can Improve Patient Selection for Clinical Trials in Localized Clear Cell Renal Cell Carcinoma |
title_full | Computerized Image Analysis of Tumor Cell Nuclear Morphology Can Improve Patient Selection for Clinical Trials in Localized Clear Cell Renal Cell Carcinoma |
title_fullStr | Computerized Image Analysis of Tumor Cell Nuclear Morphology Can Improve Patient Selection for Clinical Trials in Localized Clear Cell Renal Cell Carcinoma |
title_full_unstemmed | Computerized Image Analysis of Tumor Cell Nuclear Morphology Can Improve Patient Selection for Clinical Trials in Localized Clear Cell Renal Cell Carcinoma |
title_short | Computerized Image Analysis of Tumor Cell Nuclear Morphology Can Improve Patient Selection for Clinical Trials in Localized Clear Cell Renal Cell Carcinoma |
title_sort | computerized image analysis of tumor cell nuclear morphology can improve patient selection for clinical trials in localized clear cell renal cell carcinoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737492/ https://www.ncbi.nlm.nih.gov/pubmed/33343995 http://dx.doi.org/10.4103/jpi.jpi_13_20 |
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