Review
. 2021 Oct; :.
doi: 10.1038/s41379-021-00919-2.

Digital pathology and artificial intelligence in translational medicine and clinical practice

Vipul Baxi 1 Robin Edwards 2 Michael Montalto 3 Saurabh Saha 2 
Affiliations
  • PMID: 34611303
  •     124 References

Abstract

Traditional pathology approaches have played an integral role in the delivery of diagnosis, semi-quantitative or qualitative assessment of protein expression, and classification of disease. Technological advances and the increased focus on precision medicine have recently paved the way for the development of digital pathology-based approaches for quantitative pathologic assessments, namely whole slide imaging and artificial intelligence (AI)-based solutions, allowing us to explore and extract information beyond human visual perception. Within the field of immuno-oncology, the application of such methodologies in drug development and translational research have created invaluable opportunities for deciphering complex pathophysiology and the discovery of novel biomarkers and drug targets. With an increasing number of treatment options available for any given disease, practitioners face the growing challenge of selecting the most appropriate treatment for each patient. The ever-increasing utilization of AI-based approaches substantially expands our understanding of the tumor microenvironment, with digital approaches to patient stratification and selection for diagnostic assays supporting the identification of the optimal treatment regimen based on patient profiles. This review provides an overview of the opportunities and limitations around implementing AI-based methods in biomarker discovery and patient selection and discusses how advances in digital pathology and AI should be considered in the current landscape of translational medicine, touching on challenges this technology may face if adopted in clinical settings. The traditional role of pathologists in delivering accurate diagnoses or assessing biomarkers for companion diagnostics may be enhanced in precision, reproducibility, and scale by AI-powered analysis tools.

Novel technologies and emerging biomarkers for personalized cancer immunotherapy.
Jianda Yuan, Priti S Hegde, +16 authors, Bernard A Fox.
J Immunother Cancer, 2016 Jan 21; 4. PMID: 26788324    Free PMC article.
Highly Cited. Review.
Digital pathology and image analysis in tissue biomarker research.
Peter W Hamilton, Peter Bankhead, +5 authors, Manuel Salto-Tellez.
Methods, 2014 Jul 19; 70(1). PMID: 25034370
Review.
Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer.
Hossein Borghaei, Luis Paz-Ares, +25 authors, Julie R Brahmer.
N Engl J Med, 2015 Sep 29; 373(17). PMID: 26412456    Free PMC article.
Highly Cited.
Automated image analysis of NSCLC biopsies to predict response to anti-PD-L1 therapy.
Sonja Althammer, Tze Heng Tan, +14 authors, Keith E Steele.
J Immunother Cancer, 2019 May 08; 7(1). PMID: 31060602    Free PMC article.
Deciphering the immune microenvironment of a tissue by digital imaging and cognition network.
A Lopès, Al H Cassé, +7 authors, B Dumas.
Sci Rep, 2018 Nov 14; 8(1). PMID: 30420722    Free PMC article.
Diagnostic Immunohistochemistry: What Can Go Wrong and How to Prevent It.
Allen M Gown.
Arch Pathol Lab Med, 2016 Aug 31; 140(9). PMID: 27575264
Review.
Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057).
Leora Horn, David R Spigel, +26 authors, Wilfried E E Eberhardt.
J Clin Oncol, 2017 Oct 13; 35(35). PMID: 29023213    Free PMC article.
Highly Cited.
Classification and mutation prediction from non-small cell lung cancer histopathology images using deep learning.
Nicolas Coudray, Paolo Santiago Ocampo, +6 authors, Aristotelis Tsirigos.
Nat Med, 2018 Sep 19; 24(10). PMID: 30224757
Highly Cited.
Quantitative Characterization of CD8+ T Cell Clustering and Spatial Heterogeneity in Solid Tumors.
Chang Gong, Robert A Anders, +7 authors, Aleksander S Popel.
Front Oncol, 2019 Jan 23; 8. PMID: 30666298    Free PMC article.
Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer.
Scott J Antonia, Augusto Villegas, +28 authors, PACIFIC Investigators.
N Engl J Med, 2017 Sep 09; 377(20). PMID: 28885881
Highly Cited.
Deep learning-based classification of mesothelioma improves prediction of patient outcome.
Pierre Courtiol, Charles Maussion, +14 authors, Thomas Clozel.
Nat Med, 2019 Oct 09; 25(10). PMID: 31591589
Artificial Intelligence and Digital Pathology: Challenges and Opportunities.
Hamid Reza Tizhoosh, Liron Pantanowitz.
J Pathol Inform, 2019 Jan 05; 9. PMID: 30607305    Free PMC article.
Highly Cited. Review.
High efficacy of pre-operative trastuzumab combined with paclitaxel following doxorubicin & cyclophosphamide in operable breast cancer.
Shani Paluch-Shimon, Ido Wolf, +8 authors, Bella Kaufman.
Acta Oncol, 2008 Jul 09; 47(8). PMID: 18607846
Recent developments in multiplexing techniques for immunohistochemistry.
Angela R Dixon, Cédric Bathany, +3 authors, Shuichi Takayama.
Expert Rev Mol Diagn, 2015 Aug 21; 15(9). PMID: 26289603    Free PMC article.
Review.
Interobserver variability in histologic evaluation of radical prostatectomy between central and local pathologists: findings of TAX 3501 multinational clinical trial.
George J Netto, Mario Eisenberger, Jonathan I Epstein, TAX 3501 Trial Investigators.
Urology, 2010 Dec 15; 77(5). PMID: 21146858    Free PMC article.
Introduction to digital pathology and computer-aided pathology.
Soojeong Nam, Yosep Chong, +5 authors, Heounjeong Go.
J Pathol Transl Med, 2020 Feb 13; 54(2). PMID: 32045965    Free PMC article.
Review.
Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer.
Peter Schmid, Sylvia Adams, +16 authors, IMpassion130 Trial Investigators.
N Engl J Med, 2018 Oct 23; 379(22). PMID: 30345906
Highly Cited.
Evaluating tumor heterogeneity in immunohistochemistry-stained breast cancer tissue.
Steven J Potts, Joseph S Krueger, +4 authors, Holger Lange.
Lab Invest, 2012 Jul 18; 92(9). PMID: 22801299
Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial.
Jonathan E Rosenberg, Jean Hoffman-Censits, +28 authors, Robert Dreicer.
Lancet, 2016 Mar 10; 387(10031). PMID: 26952546    Free PMC article.
Highly Cited.
HannaH phase III randomised study: Association of total pathological complete response with event-free survival in HER2-positive early breast cancer treated with neoadjuvant-adjuvant trastuzumab after 2 years of treatment-free follow-up.
Christian Jackisch, Roberto Hegg, +13 authors, Xavier Pivot.
Eur J Cancer, 2016 May 23; 62. PMID: 27208905
Epithelium segmentation using deep learning in H&E-stained prostate specimens with immunohistochemistry as reference standard.
Wouter Bulten, Péter Bándi, +7 authors, Geert Litjens.
Sci Rep, 2019 Jan 31; 9(1). PMID: 30696866    Free PMC article.
International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study.
Franck Pagès, Bernhard Mlecnik, +96 authors, Jérôme Galon.
Lancet, 2018 May 15; 391(10135). PMID: 29754777
Highly Cited.
Artificial Intelligence Algorithms to Assess Hormonal Status From Tissue Microarrays in Patients With Breast Cancer.
Gil Shamai, Yoav Binenbaum, +3 authors, Ron Kimmel.
JAMA Netw Open, 2019 Jul 28; 2(7). PMID: 31348505    Free PMC article.
Comprehensive Immunohistochemistry: Digital, Analytical and Integrated.
Arvydas Laurinavicius, Benoit Plancoulaine, Paulette Herlin, Aida Laurinaviciene.
Pathobiology, 2016 Apr 23; 83(2-3). PMID: 27101138
Immunohistochemistry as an important tool in biomarkers detection and clinical practice.
Leandro Luongo de Matos, Damila Cristina Trufelli, Maria Graciela Luongo de Matos, Maria Aparecida da Silva Pinhal.
Biomark Insights, 2010 Mar 10; 5. PMID: 20212918    Free PMC article.
Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer.
Julienne L Carstens, Pedro Correa de Sampaio, +6 authors, Raghu Kalluri.
Nat Commun, 2017 Apr 28; 8. PMID: 28447602    Free PMC article.
Highly Cited.
Deep learning can predict microsatellite instability directly from histology in gastrointestinal cancer.
Jakob Nikolas Kather, Alexander T Pearson, +14 authors, Tom Luedde.
Nat Med, 2019 Jun 05; 25(7). PMID: 31160815    Free PMC article.
Highly Cited.
Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial.
Roy S Herbst, Paul Baas, +16 authors, Edward B Garon.
Lancet, 2015 Dec 30; 387(10027). PMID: 26712084
Highly Cited.
Applications of machine learning in drug discovery and development.
Jessica Vamathevan, Dominic Clark, +8 authors, Shanrong Zhao.
Nat Rev Drug Discov, 2019 Apr 13; 18(6). PMID: 30976107    Free PMC article.
Highly Cited. Review.
BREAST CANCER HISTOPATHOLOGY IMAGE ANALYSIS PIPELINE FOR TUMOR PURITY ESTIMATION.
Vahid Azimi, Young Hwan Chang, +7 authors, Joe W Gray.
Proc IEEE Int Symp Biomed Imaging, 2017 Apr 01; 2017. PMID: 30364881    Free PMC article.
Protocol for development of a reporting guideline (TRIPOD-AI) and risk of bias tool (PROBAST-AI) for diagnostic and prognostic prediction model studies based on artificial intelligence.
Gary S Collins, Paula Dhiman, +10 authors, Karel Gm Moons.
BMJ Open, 2021 Jul 11; 11(7). PMID: 34244270    Free PMC article.
Preanalytic Variables and Tissue Stewardship for Reliable Next-Generation Sequencing (NGS) Clinical Analysis.
Paolo A Ascierto, Carlo Bifulco, +2 authors, Nikoletta Sidiropoulos.
J Mol Diagn, 2019 Jun 30; 21(5). PMID: 31251989
Review.
Reliability of tumor-infiltrating lymphocyte and tertiary lymphoid structure assessment in human breast cancer.
Laurence Buisseret, Christine Desmedt, +15 authors, Karen Willard-Gallo.
Mod Pathol, 2017 Jun 18; 30(9). PMID: 28621322
PD-L1 expression in gastric cancer determined by digital image analyses: pitfalls and correlation with pathologist interpretation.
Han-Na Kim, Jiryeon Jang, +8 authors, Kyoung-Mee Kim.
Virchows Arch, 2019 Aug 30; 476(2). PMID: 31463730
Barriers and facilitators to the introduction of digital pathology for diagnostic work.
Rebecca Randell, Roy A Ruddle, Darren Treanor.
Stud Health Technol Inform, 2015 Aug 12; 216. PMID: 26262089
The human-in-the-loop: an evaluation of pathologists' interaction with artificial intelligence in clinical practice.
Anna C S Bodén, Jesper Molin, +3 authors, Darren Treanor.
Histopathology, 2021 Feb 17; 79(2). PMID: 33590577
A Practical Guide to Whole Slide Imaging: A White Paper From the Digital Pathology Association.
Mark D Zarella, Douglas Bowman, +6 authors, Douglas J Hartman.
Arch Pathol Lab Med, 2018 Oct 12; 143(2). PMID: 30307746
Highly Cited. Review.
Multi-institutional TSA-amplified Multiplexed Immunofluorescence Reproducibility Evaluation (MITRE) Study.
Janis M Taube, Kristin Roman, +13 authors, Cliff Hoyt.
J Immunother Cancer, 2021 Jul 17; 9(7). PMID: 34266881    Free PMC article.
Deep Learning Based on Standard H&E Images of Primary Melanoma Tumors Identifies Patients at Risk for Visceral Recurrence and Death.
Prathamesh M Kulkarni, Eric J Robinson, +19 authors, Yvonne M Saenger.
Clin Cancer Res, 2019 Oct 23; 26(5). PMID: 31636101    Free PMC article.
Relevance of deep learning to facilitate the diagnosis of HER2 status in breast cancer.
Michel E Vandenberghe, Marietta L J Scott, +3 authors, Craig Barker.
Sci Rep, 2017 Apr 06; 7. PMID: 28378829    Free PMC article.
Deep learning outperformed 11 pathologists in the classification of histopathological melanoma images.
Achim Hekler, Jochen S Utikal, +12 authors, Titus J Brinker.
Eur J Cancer, 2019 Jul 22; 118. PMID: 31325876
American Telemedicine Association clinical guidelines for telepathology.
Liron Pantanowitz, Kim Dickinson, +12 authors, Jordana Bernard.
J Pathol Inform, 2014 Nov 08; 5(1). PMID: 25379345    Free PMC article.
Multiplexed immunohistochemistry, imaging, and quantitation: a review, with an assessment of Tyramide signal amplification, multispectral imaging and multiplex analysis.
Edward C Stack, Chichung Wang, Kristin A Roman, Clifford C Hoyt.
Methods, 2014 Sep 23; 70(1). PMID: 25242720
Highly Cited. Review.
Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma.
Zipei Feng, Sachin Puri, +7 authors, Bernard A Fox.
J Immunother Cancer, 2015 Oct 27; 3. PMID: 26500776    Free PMC article.
Deep learning in histopathology: the path to the clinic.
Jeroen van der Laak, Geert Litjens, Francesco Ciompi.
Nat Med, 2021 May 16; 27(5). PMID: 33990804
Review.
Continuous measurement of breast tumour hormone receptor expression: a comparison of two computational pathology platforms.
Thomas P Ahern, Andrew H Beck, +4 authors, Rulla M Tamimi.
J Clin Pathol, 2016 Oct 13; 70(5). PMID: 27729430    Free PMC article.
Diagnostic Assessment of Deep Learning Algorithms for Detection of Lymph Node Metastases in Women With Breast Cancer.
Babak Ehteshami Bejnordi, Mitko Veta, +67 authors, Rui Venâncio.
JAMA, 2017 Dec 14; 318(22). PMID: 29234806    Free PMC article.
Highly Cited.
CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer.
Yelena Y Janjigian, Johanna Bendell, +13 authors, Dung T Le.
J Clin Oncol, 2018 Aug 16; 36(28). PMID: 30110194    Free PMC article.
Highly Cited.
Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection.
Qiang Gao, Shuang-Jian Qiu, +6 authors, Zhao-You Tang.
J Clin Oncol, 2007 Jun 20; 25(18). PMID: 17577038
Highly Cited.
Translational AI and Deep Learning in Diagnostic Pathology.
Ahmed Serag, Adrian Ion-Margineanu, +5 authors, Peter Hamilton.
Front Med (Lausanne), 2019 Oct 22; 6. PMID: 31632973    Free PMC article.
Review.
Systems pathology by multiplexed immunohistochemistry and whole-slide digital image analysis.
Sami Blom, Lassi Paavolainen, +7 authors, Teijo Pellinen.
Sci Rep, 2017 Nov 16; 7(1). PMID: 29138507    Free PMC article.
Highly Cited.
Dynamics of allograft fibrosis in pediatric liver transplantation.
C Venturi, C Sempoux, +4 authors, R Reding.
Am J Transplant, 2014 Jun 18; 14(7). PMID: 24934832
Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC.
Paul C Tumeh, Matthew D Hellmann, +31 authors, Adil Daud.
Cancer Immunol Res, 2017 Apr 16; 5(5). PMID: 28411193    Free PMC article.
Highly Cited.
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer.
Martin Reck, Delvys Rodríguez-Abreu, +16 authors, KEYNOTE-024 Investigators.
N Engl J Med, 2016 Oct 11; 375(19). PMID: 27718847
Highly Cited.
Classification and mutation prediction based on histopathology H&E images in liver cancer using deep learning.
Mingyu Chen, Bin Zhang, +6 authors, Xiujun Cai.
NPJ Precis Oncol, 2020 Jun 19; 4. PMID: 32550270    Free PMC article.
Not Just Digital Pathology, Intelligent Digital Pathology.
Balazs Acs, David L Rimm.
JAMA Oncol, 2018 Feb 03; 4(3). PMID: 29392271
Computational pathology definitions, best practices, and recommendations for regulatory guidance: a white paper from the Digital Pathology Association.
Esther Abels, Liron Pantanowitz, +9 authors, Cleopatra Kozlowski.
J Pathol, 2019 Jul 30; 249(3). PMID: 31355445    Free PMC article.
Review.
The application of discovery toxicology and pathology towards the design of safer pharmaceutical lead candidates.
Jeffrey A Kramer, John E Sagartz, Dale L Morris.
Nat Rev Drug Discov, 2007 Jul 24; 6(8). PMID: 17643090
Review.
Pathology is a necessary and informative tool in oncology clinical trials.
Iris D Nagtegaal, Nicholas P West, J Han J M van Krieken, Phil Quirke.
J Pathol, 2013 Sep 17; 232(2). PMID: 24037805
Review.
Histo-genomics: digital pathology at the forefront of precision medicine.
Ivraym Barsoum, Eriny Tawedrous, Hala Faragalla, George M Yousef.
Diagnosis (Berl), 2019 Mar 05; 6(3). PMID: 30827078
Review.
Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial.
Achim Rittmeyer, Fabrice Barlesi, +23 authors, OAK Study Group.
Lancet, 2016 Dec 17; 389(10066). PMID: 27979383    Free PMC article.
Highly Cited.
The use of digital pathology and image analysis in clinical trials.
Robert Pell, Karin Oien, +6 authors, UK National Cancer Research Institute (NCRI) Cellular-Molecular Pathology (CM-Path) quality assurance working group.
J Pathol Clin Res, 2019 Feb 16; 5(2). PMID: 30767396    Free PMC article.
A radiomics approach to assess tumour-infiltrating CD8 cells and response to anti-PD-1 or anti-PD-L1 immunotherapy: an imaging biomarker, retrospective multicohort study.
Roger Sun, Elaine Johanna Limkin, +16 authors, Charles Ferté.
Lancet Oncol, 2018 Aug 19; 19(9). PMID: 30120041
Highly Cited.
Hidden Variables in Deep Learning Digital Pathology and Their Potential to Cause Batch Effects: Prediction Model Study.
Max Schmitt, Roman Christoph Maron, +14 authors, Titus Josef Brinker.
J Med Internet Res, 2021 Feb 03; 23(2). PMID: 33528370    Free PMC article.
Predicting treatment response to neoadjuvant chemoradiotherapy in local advanced rectal cancer by biopsy digital pathology image features.
Fang Zhang, Su Yao, +7 authors, Zaiyi Liu.
Clin Transl Med, 2020 Jul 01; 10(2). PMID: 32594660    Free PMC article.
Artificial intelligence in digital pathology - new tools for diagnosis and precision oncology.
Kaustav Bera, Kurt A Schalper, +2 authors, Anant Madabhushi.
Nat Rev Clin Oncol, 2019 Aug 11; 16(11). PMID: 31399699    Free PMC article.
Highly Cited. Review.
Pembrolizumab for the treatment of non-small-cell lung cancer.
Edward B Garon, Naiyer A Rizvi, +25 authors, KEYNOTE-001 Investigators.
N Engl J Med, 2015 Apr 22; 372(21). PMID: 25891174
Highly Cited.
Digital pathology and image analysis for robust high-throughput quantitative assessment of Alzheimer disease neuropathologic changes.
Janna Hackett Neltner, Erin Lynn Abner, +4 authors, Peter T Nelson.
J Neuropathol Exp Neurol, 2012 Nov 14; 71(12). PMID: 23147505    Free PMC article.
Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data.
Monique Maas, Patty J Nelemans, +15 authors, Geerard L Beets.
Lancet Oncol, 2010 Aug 10; 11(9). PMID: 20692872
Highly Cited.
Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer.
Eiichi Sato, Sara H Olson, +15 authors, Kunle Odunsi.
Proc Natl Acad Sci U S A, 2005 Dec 14; 102(51). PMID: 16344461    Free PMC article.
Highly Cited.
Prognostic role and predictors of complete pathologic response to neoadjuvant chemotherapy in primary unresectable ovarian cancer.
Marco Petrillo, Gian Franco Zannoni, +6 authors, Anna Fagotti.
Am J Obstet Gynecol, 2014 Jun 24; 211(6). PMID: 24954656
Digital pathology and computational image analysis in nephropathology.
Laura Barisoni, Kyle J Lafata, +2 authors, Ulysses G J Balis.
Nat Rev Nephrol, 2020 Aug 28; 16(11). PMID: 32848206    Free PMC article.
Review.
Accurate and reproducible invasive breast cancer detection in whole-slide images: A Deep Learning approach for quantifying tumor extent.
Angel Cruz-Roa, Hannah Gilmore, +6 authors, Anant Madabhushi.
Sci Rep, 2017 Apr 19; 7. PMID: 28418027    Free PMC article.
Highly Cited.
Quantitative Image Analysis of Human Epidermal Growth Factor Receptor 2 Immunohistochemistry for Breast Cancer: Guideline From the College of American Pathologists.
Marilyn M Bui, Michael W Riben, +11 authors, M Elizabeth Hammond.
Arch Pathol Lab Med, 2019 Jan 16; 143(10). PMID: 30645156    Free PMC article.
Integrating mutation variant allele frequency into clinical practice in myeloid malignancies.
David A Sallman, Eric Padron.
Hematol Oncol Stem Cell Ther, 2016 May 18; 9(3). PMID: 27187622
Review.
PD-L1 immunohistochemistry in clinical diagnostics of lung cancer: inter-pathologist variability is higher than assay variability.
Hans Brunnström, Anna Johansson, +6 authors, Patrick Micke.
Mod Pathol, 2017 Jul 01; 30(10). PMID: 28664936
Highly Cited.
A Prospective, Multi-institutional, Pathologist-Based Assessment of 4 Immunohistochemistry Assays for PD-L1 Expression in Non-Small Cell Lung Cancer.
David L Rimm, Gang Han, +17 authors, Ignacio I Wistuba.
JAMA Oncol, 2017 Mar 10; 3(8). PMID: 28278348    Free PMC article.
Highly Cited.
Society of Toxicologic Pathology position paper on pathology image data: compliance with 21 CFR Parts 58 and 11.
Darrell L Tuomari, Ramon K Kemp, +6 authors, Society of Toxicologic Pathology.
Toxicol Pathol, 2007 May 03; 35(3). PMID: 17474067
Programmed Death-Ligand 1 Immunohistochemistry Testing: A Review of Analytical Assays and Clinical Implementation in Non-Small-Cell Lung Cancer.
Reinhard Büttner, John R Gosney, +11 authors, Ming-Sound Tsao.
J Clin Oncol, 2017 Oct 21; 35(34). PMID: 29053400
Highly Cited. Review.
Deep neural network models for computational histopathology: A survey.
Chetan L Srinidhi, Ozan Ciga, Anne L Martel.
Med Image Anal, 2020 Oct 14; 67. PMID: 33049577    Free PMC article.
Review.
Complete Digital Pathology for Routine Histopathology Diagnosis in a Multicenter Hospital Network.
Juan Antonio Retamero, Jose Aneiros-Fernandez, Raimundo G Del Moral.
Arch Pathol Lab Med, 2019 Jul 12; 144(2). PMID: 31295015
Whole slide imaging equivalency and efficiency study: experience at a large academic center.
Matthew G Hanna, Victor E Reuter, +17 authors, S Joseph Sirintrapun.
Mod Pathol, 2019 Feb 20; 32(7). PMID: 30778169
Mapping spatial heterogeneity in the tumor microenvironment: a new era for digital pathology.
Andreas Heindl, Sidra Nawaz, Yinyin Yuan.
Lab Invest, 2015 Jan 20; 95(4). PMID: 25599534
Review.
Prognostic Factors for Checkpoint Inhibitor Based Immunotherapy: An Update With New Evidences.
Xinyu Yan, Shouyue Zhang, +3 authors, Heng Xu.
Front Pharmacol, 2018 Oct 09; 9. PMID: 30294272    Free PMC article.
Review.
Scientific and Regulatory Policy Committee (SRPC) paper: validation of digital pathology systems in the regulated nonclinical environment.
Richard E Long, Adam Smith, +6 authors, Amanda Lowe.
Toxicol Pathol, 2012 Jun 23; 41(1). PMID: 22723045
Pan-Tumor Pathologic Scoring of Response to PD-(L)1 Blockade.
Julie E Stein, Evan J Lipson, +12 authors, Janis M Taube.
Clin Cancer Res, 2019 Nov 02; 26(3). PMID: 31672770    Free PMC article.
Benchmarking of Whole Exome Sequencing and Ad Hoc Designed Panels for Genetic Testing of Hereditary Cancer.
Lídia Feliubadaló, Raúl Tonda, +18 authors, Conxi Lázaro.
Sci Rep, 2017 Jan 05; 7. PMID: 28050010    Free PMC article.
Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC).
T R Cottrell, E D Thompson, +27 authors, J M Taube.
Ann Oncol, 2018 Jul 10; 29(8). PMID: 29982279    Free PMC article.
Highly Cited.
Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial.
Louis Fehrenbacher, Alexander Spira, +16 authors, POPLAR Study Group.
Lancet, 2016 Mar 14; 387(10030). PMID: 26970723
Highly Cited.
LAG3: The Biological Processes That Motivate Targeting This Immune Checkpoint Molecule in Human Cancer.
Cinzia Solinas, Edoardo Migliori, Pushpamali De Silva, Karen Willard-Gallo.
Cancers (Basel), 2019 Aug 23; 11(8). PMID: 31434339    Free PMC article.
Review.
Who is afraid of black box algorithms? On the epistemological and ethical basis of trust in medical AI.
Juan Manuel Durán, Karin Rolanda Jongsma.
J Med Ethics, 2021 Mar 20;. PMID: 33737318
PD-L1 Immunohistochemistry Comparability Study in Real-Life Clinical Samples: Results of Blueprint Phase 2 Project.
Ming Sound Tsao, Keith M Kerr, +25 authors, Fred R Hirsch.
J Thorac Oncol, 2018 May 26; 13(9). PMID: 29800747    Free PMC article.
Highly Cited.
Identification and use of biomarkers in treatment strategies for triple-negative breast cancer subtypes.
Brian D Lehmann, Jennifer A Pietenpol.
J Pathol, 2013 Oct 12; 232(2). PMID: 24114677    Free PMC article.
Highly Cited. Review.
Tumor purity as a prognosis and immunotherapy relevant feature in gastric cancer.
Zhe Gong, Jieyun Zhang, Weijian Guo.
Cancer Med, 2020 Oct 09; 9(23). PMID: 33030278    Free PMC article.
Digital pathology and artificial intelligence will be key to supporting clinical and academic cellular pathology through COVID-19 and future crises: the PathLAKE consortium perspective.
Lisa Browning, Richard Colling, +6 authors, Clare Verrill.
J Clin Pathol, 2020 Jul 06; 74(7). PMID: 32620678    Free PMC article.
Review.
Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study.
Corey J Langer, Shirish M Gadgeel, +17 authors, KEYNOTE-021 investigators.
Lancet Oncol, 2016 Oct 18; 17(11). PMID: 27745820    Free PMC article.
Highly Cited.
Central pathology review for phase III clinical trials: the enabling effect of virtual microscopy.
Pawel Mroz, Anil V Parwani, Piotr Kulesza.
Arch Pathol Lab Med, 2013 Apr 03; 137(4). PMID: 23544938
Deep learning for digital pathology image analysis: A comprehensive tutorial with selected use cases.
Andrew Janowczyk, Anant Madabhushi.
J Pathol Inform, 2016 Aug 27; 7. PMID: 27563488    Free PMC article.
Highly Cited.
CD4 and CD8 T lymphocyte interplay in controlling tumor growth.
Dmitrij Ostroumov, Nora Fekete-Drimusz, +2 authors, Norman Woller.
Cell Mol Life Sci, 2017 Oct 17; 75(4). PMID: 29032503    Free PMC article.
Review.
Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma.
Joaquim Bellmunt, Ronald de Wit, +18 authors, KEYNOTE-045 Investigators.
N Engl J Med, 2017 Feb 18; 376(11). PMID: 28212060    Free PMC article.
Highly Cited.
Quality control stress test for deep learning-based diagnostic model in digital pathology.
Birgid Schömig-Markiefka, Alexey Pryalukhin, +8 authors, Yuri Tolkach.
Mod Pathol, 2021 Jun 26;. PMID: 34168282
Systematic analysis of breast cancer morphology uncovers stromal features associated with survival.
Andrew H Beck, Ankur R Sangoi, +6 authors, Daphne Koller.
Sci Transl Med, 2011 Nov 11; 3(108). PMID: 22072638
Highly Cited.
Measuring multiple parameters of CD8+ tumor-infiltrating lymphocytes in human cancers by image analysis.
Keith E Steele, Tze Heng Tan, +13 authors, Tobias Wiestler.
J Immunother Cancer, 2018 Mar 08; 6(1). PMID: 29510739    Free PMC article.
Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis.
Patricia Cortazar, Lijun Zhang, +34 authors, Gunter von Minckwitz.
Lancet, 2014 Feb 18; 384(9938). PMID: 24529560
Highly Cited. Review.
Automated image analysis method for detecting and quantifying macrovesicular steatosis in hematoxylin and eosin-stained histology images of human livers.
Nir I Nativ, Alvin I Chen, +8 authors, Martin L Yarmush.
Liver Transpl, 2013 Dec 18; 20(2). PMID: 24339411    Free PMC article.
Noninvasive detection of macrophage activation with single-cell resolution through machine learning.
Nicolas Pavillon, Alison J Hobro, Shizuo Akira, Nicholas I Smith.
Proc Natl Acad Sci U S A, 2018 Mar 08; 115(12). PMID: 29511099    Free PMC article.
Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial.
James L Gulley, Arun Rajan, +11 authors, Karen Kelly.
Lancet Oncol, 2017 Apr 05; 18(5). PMID: 28373005    Free PMC article.
Highly Cited.
Clinical Trials for Artificial Intelligence in Cancer Diagnosis: A Cross-Sectional Study of Registered Trials in ClinicalTrials.gov.
Jingsi Dong, Yingcai Geng, +4 authors, Yonggang Zhang.
Front Oncol, 2020 Oct 13; 10. PMID: 33042806    Free PMC article.
Introduction to Digital Image Analysis in Whole-slide Imaging: A White Paper from the Digital Pathology Association.
Famke Aeffner, Mark D Zarella, +11 authors, Douglas Bowman.
J Pathol Inform, 2019 Apr 16; 10. PMID: 30984469    Free PMC article.
Highly Cited. Review.
Classification of breast cancer histology images using Convolutional Neural Networks.
Teresa Araújo, Guilherme Aresta, +5 authors, Aurélio Campilho.
PLoS One, 2017 Jun 02; 12(6). PMID: 28570557    Free PMC article.
Highly Cited.
Precision immunoprofiling by image analysis and artificial intelligence.
Viktor H Koelzer, Korsuk Sirinukunwattana, Jens Rittscher, Kirsten D Mertz.
Virchows Arch, 2018 Nov 25; 474(4). PMID: 30470933    Free PMC article.
Review.
HistoQC: An Open-Source Quality Control Tool for Digital Pathology Slides.
Andrew Janowczyk, Ren Zuo, +2 authors, Anant Madabhushi.
JCO Clin Cancer Inform, 2019 Apr 17; 3. PMID: 30990737    Free PMC article.
Pathologist Concordance for Ovarian Carcinoma Subtype Classification and Identification of Relevant Histologic Features Using Microscope and Whole Slide Imaging: A Multisite Observer Study.
Marios A Gavrielides, Brigitte M Ronnett, +10 authors, Jeffrey D Seidman.
Arch Pathol Lab Med, 2021 Feb 27;. PMID: 33635941
First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer.
David P Carbone, Martin Reck, +27 authors, CheckMate 026 Investigators.
N Engl J Med, 2017 Jun 22; 376(25). PMID: 28636851    Free PMC article.
Highly Cited.
The estimation of tumor cell percentage for molecular testing by pathologists is not accurate.
Alexander J J Smits, J Alain Kummer, +8 authors, Aryan Vink.
Mod Pathol, 2013 Jul 28; 27(2). PMID: 23887293
Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer.
S T Martin, H M Heneghan, D C Winter.
Br J Surg, 2012 Mar 01; 99(7). PMID: 22362002
Highly Cited. Systematic Review.
Prediction of recurrence in early stage non-small cell lung cancer using computer extracted nuclear features from digital H&E images.
Xiangxue Wang, Andrew Janowczyk, +5 authors, Anant Madabhushi.
Sci Rep, 2017 Oct 21; 7(1). PMID: 29051570    Free PMC article.
Comparison of Biomarker Modalities for Predicting Response to PD-1/PD-L1 Checkpoint Blockade: A Systematic Review and Meta-analysis.
Steve Lu, Julie E Stein, +11 authors, Janis M Taube.
JAMA Oncol, 2019 Jul 19; 5(8). PMID: 31318407    Free PMC article.
Highly Cited.
Pathology in drug discovery and development.
Adrian M Jubb, Hartmut Koeppen, Jorge S Reis-Filho.
J Pathol, 2013 Oct 15; 232(2). PMID: 24122335
The Society for Immunotherapy of Cancer statement on best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) staining and validation.
Janis M Taube, Guray Akturk, +25 authors, Society for Immunotherapy of Cancer (SITC) Pathology Task Force..
J Immunother Cancer, 2020 May 18; 8(1). PMID: 32414858    Free PMC article.
Validating whole slide imaging for diagnostic purposes in pathology: guideline from the College of American Pathologists Pathology and Laboratory Quality Center.
Liron Pantanowitz, John H Sinard, +8 authors, College of American Pathologists Pathology and Laboratory Quality Center.
Arch Pathol Lab Med, 2013 May 03; 137(12). PMID: 23634907    Free PMC article.
Highly Cited. Review.
Digital pathology in drug discovery and development: multisite integration.
Steven J Potts.
Drug Discov Today, 2009 Jul 15; 14(19-20). PMID: 19596461
Review.
International Clinical Guidelines for the Adoption of Digital Pathology: A Review of Technical Aspects.
Marcial García-Rojo.
Pathobiology, 2016 Apr 23; 83(2-3). PMID: 27100834
Review.
The microenvironmental niche in classic Hodgkin lymphoma is enriched for CTLA-4-positive T cells that are PD-1-negative.
Sanjay S Patel, Jason L Weirather, +6 authors, Scott J Rodig.
Blood, 2019 Nov 08; 134(23). PMID: 31697809    Free PMC article.