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.

Details

Title
Automated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma
Author
Moore, Michael R 1 ; Friesner, Isabel D 2 ; Rizk, Emanuelle M 1 ; Fullerton, Benjamin T 1 ; Mondal Manas 1 ; Trager, Megan H 3 ; Mendelson, Karen 4 ; Chikeka Ijeuru 5 ; Kurc Tahsin 6 ; Gupta Rajarsi 6 ; Rohr, Bethany R 7 ; Robinson, Eric J 8 ; Acs Balazs 9 ; Chang, Rui 10 ; Kluger, Harriet 11 ; Taback Bret 12 ; Geskin, Larisa J 5 ; Horst, Basil 13 ; Gardner, Kevin 14 ; Niedt, George 5 ; Celebi, Julide T 4 ; Gartrell-Corrado, Robyn D 15 ; Messina, Jane 16 ; Ferringer Tammie 17 ; Rimm, David L 18 ; Saltz, Joel 6 ; Wang, Jing 19 ; Vanguri Rami 14 ; Saenger, Yvonne M 1 

 Columbia University Irving Medical Center, Department of Medicine, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729) 
 NYU School of Medicine, NYULMC, Department of Anesthesiology, Perioperative Care and Pain Medicine, New York, USA (GRID:grid.137628.9) (ISNI:0000 0004 1936 8753) 
 Columbia University, Vagelos College of Physicians and Surgeons, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729) 
 Icahn School of Medicine at Mount Sinai, Department of Dermatology, Pathology, and Oncological Sciences, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351) 
 Columbia University Irving Medical Center, Department of Dermatology, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729) 
 Stony Brook Medicine, Department of Biomedical Informatics, Stony Brook, USA (GRID:grid.459987.e) 
 University Hospitals Cleveland Medical Center/Case Western Reserve University School of Medicine, Department of Dermatology, Cleveland, USA (GRID:grid.67105.35) (ISNI:0000 0001 2164 3847) 
 Oregon Health and Science University School of Medicine, Portland, USA (GRID:grid.5288.7) (ISNI:0000 0000 9758 5690) 
 Yale School of Medicine, Department of Pathology, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710); Karolinska Institute, Department of Oncology and Pathology, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626) 
10  University of Arizona, Department of Neurology, Tucson, USA (GRID:grid.134563.6) (ISNI:0000 0001 2168 186X) 
11  Yale School of Medicine, Department of Medicine, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710) 
12  Columbia University Irving Medical Center, Department of Surgery, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729) 
13  University of British Columbia, Department of Pathology, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830) 
14  Columbia University Irving Medical Center, Department of Pathology, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729) 
15  Columbia University Irving Medical Center, Department of Pediatrics, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729) 
16  The Moffitt Cancer Center, Department of Cutaneous Oncology, Tampa, USA (GRID:grid.468198.a) (ISNI:0000 0000 9891 5233) 
17  Geisinger Health System, Department of Pathology, Danville, USA (GRID:grid.280776.c) (ISNI:0000 0004 0394 1447) 
18  Yale School of Medicine, Department of Pathology, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710) 
19  NYU School of Medicine, NYULMC, Department of Anesthesiology, Perioperative Care and Pain Medicine, New York, USA (GRID:grid.137628.9) (ISNI:0000 0004 1936 8753); NYU School of Medicine, Department of Neuroscience and Physiology, New York, USA (GRID:grid.137628.9) (ISNI:0000 0004 1936 8753) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2485324971
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.