Automated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma

Abstract Accurate prognostic biomarkers in early-stage melanoma are urgently needed to stratify patients for clinical trials of adjuvant therapy. We applied a previously developed open source deep learning algorithm to detect tumor-infiltrating lymphocytes (TILs) in hematoxylin and eosin (H&E) i...

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Autores principales: Michael R. Moore, Isabel D. Friesner, Emanuelle M. Rizk, Benjamin T. Fullerton, Manas Mondal, Megan H. Trager, Karen Mendelson, Ijeuru Chikeka, Tahsin Kurc, Rajarsi Gupta, Bethany R. Rohr, Eric J. Robinson, Balazs Acs, Rui Chang, Harriet Kluger, Bret Taback, Larisa J. Geskin, Basil Horst, Kevin Gardner, George Niedt, Julide T. Celebi, Robyn D. Gartrell-Corrado, Jane Messina, Tammie Ferringer, David L. Rimm, Joel Saltz, Jing Wang, Rami Vanguri, Yvonne M. Saenger
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:8d415bf272d94264979172564903d21c2021-12-02T14:06:51ZAutomated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma10.1038/s41598-021-82305-12045-2322https://doaj.org/article/8d415bf272d94264979172564903d21c2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82305-1https://doaj.org/toc/2045-2322Abstract Accurate prognostic biomarkers in early-stage melanoma are urgently needed to stratify patients for clinical trials of adjuvant therapy. We applied a previously developed open source deep learning algorithm to detect tumor-infiltrating lymphocytes (TILs) in hematoxylin and eosin (H&E) images of early-stage melanomas. We tested whether automated digital (TIL) analysis (ADTA) improved accuracy of prediction of disease specific survival (DSS) based on current pathology standards. ADTA was applied to a training cohort (n = 80) and a cutoff value was defined based on a Receiver Operating Curve. ADTA was then applied to a validation cohort (n = 145) and the previously determined cutoff value was used to stratify high and low risk patients, as demonstrated by Kaplan–Meier analysis (p ≤ 0.001). Multivariable Cox proportional hazards analysis was performed using ADTA, depth, and ulceration as co-variables and showed that ADTA contributed to DSS prediction (HR: 4.18, CI 1.51–11.58, p = 0.006). ADTA provides an effective and attainable assessment of TILs and should be further evaluated in larger studies for inclusion in staging algorithms.Michael R. MooreIsabel D. FriesnerEmanuelle M. RizkBenjamin T. FullertonManas MondalMegan H. TragerKaren MendelsonIjeuru ChikekaTahsin KurcRajarsi GuptaBethany R. RohrEric J. RobinsonBalazs AcsRui ChangHarriet KlugerBret TabackLarisa J. GeskinBasil HorstKevin GardnerGeorge NiedtJulide T. CelebiRobyn D. Gartrell-CorradoJane MessinaTammie FerringerDavid L. RimmJoel SaltzJing WangRami VanguriYvonne M. SaengerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Michael R. Moore
Isabel D. Friesner
Emanuelle M. Rizk
Benjamin T. Fullerton
Manas Mondal
Megan H. Trager
Karen Mendelson
Ijeuru Chikeka
Tahsin Kurc
Rajarsi Gupta
Bethany R. Rohr
Eric J. Robinson
Balazs Acs
Rui Chang
Harriet Kluger
Bret Taback
Larisa J. Geskin
Basil Horst
Kevin Gardner
George Niedt
Julide T. Celebi
Robyn D. Gartrell-Corrado
Jane Messina
Tammie Ferringer
David L. Rimm
Joel Saltz
Jing Wang
Rami Vanguri
Yvonne M. Saenger
Automated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma
description Abstract Accurate prognostic biomarkers in early-stage melanoma are urgently needed to stratify patients for clinical trials of adjuvant therapy. We applied a previously developed open source deep learning algorithm to detect tumor-infiltrating lymphocytes (TILs) in hematoxylin and eosin (H&E) images of early-stage melanomas. We tested whether automated digital (TIL) analysis (ADTA) improved accuracy of prediction of disease specific survival (DSS) based on current pathology standards. ADTA was applied to a training cohort (n = 80) and a cutoff value was defined based on a Receiver Operating Curve. ADTA was then applied to a validation cohort (n = 145) and the previously determined cutoff value was used to stratify high and low risk patients, as demonstrated by Kaplan–Meier analysis (p ≤ 0.001). Multivariable Cox proportional hazards analysis was performed using ADTA, depth, and ulceration as co-variables and showed that ADTA contributed to DSS prediction (HR: 4.18, CI 1.51–11.58, p = 0.006). ADTA provides an effective and attainable assessment of TILs and should be further evaluated in larger studies for inclusion in staging algorithms.
format article
author Michael R. Moore
Isabel D. Friesner
Emanuelle M. Rizk
Benjamin T. Fullerton
Manas Mondal
Megan H. Trager
Karen Mendelson
Ijeuru Chikeka
Tahsin Kurc
Rajarsi Gupta
Bethany R. Rohr
Eric J. Robinson
Balazs Acs
Rui Chang
Harriet Kluger
Bret Taback
Larisa J. Geskin
Basil Horst
Kevin Gardner
George Niedt
Julide T. Celebi
Robyn D. Gartrell-Corrado
Jane Messina
Tammie Ferringer
David L. Rimm
Joel Saltz
Jing Wang
Rami Vanguri
Yvonne M. Saenger
author_facet Michael R. Moore
Isabel D. Friesner
Emanuelle M. Rizk
Benjamin T. Fullerton
Manas Mondal
Megan H. Trager
Karen Mendelson
Ijeuru Chikeka
Tahsin Kurc
Rajarsi Gupta
Bethany R. Rohr
Eric J. Robinson
Balazs Acs
Rui Chang
Harriet Kluger
Bret Taback
Larisa J. Geskin
Basil Horst
Kevin Gardner
George Niedt
Julide T. Celebi
Robyn D. Gartrell-Corrado
Jane Messina
Tammie Ferringer
David L. Rimm
Joel Saltz
Jing Wang
Rami Vanguri
Yvonne M. Saenger
author_sort Michael R. Moore
title Automated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma
title_short Automated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma
title_full Automated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma
title_fullStr Automated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma
title_full_unstemmed Automated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma
title_sort automated digital til analysis (adta) adds prognostic value to standard assessment of depth and ulceration in primary melanoma
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/8d415bf272d94264979172564903d21c
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