The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma
Authors: Xiaoxi Pan, Khalid AbdulJabbar, Jose Coelho-Lima, Anca-Ioana Grapa, Hanyun Zhang, Alvin Ho Kwan Cheung, Juvenal Baena, Takahiro Karasaki, Claire Rachel Wilson, Marco Sereno, Selvaraju Veeriah, Sarah J. Aitken, Allan Hackshaw, Andrew G. Nicholson, Mariam Jamal-Hanjani, John Le Quesne, Sam M. Janes, Anne-Marie Hacker, Abigail Sharp, Sean Smith, Harjot Kaur Dhanda, Kitty Chan, Camilla Pilotti, Rachel Leslie, David Chuter, Mairead MacKenzie, Serena Chee, Aiman Alzetani, Eric Lim, Paulo De Sousa, Simon Jordan, Alexandra Rice, Hilgardt Raubenheimer, Harshil Bhayani, Lyn Ambrose, Anand Devaraj, Hema Chavan, Sofina Begum, Silviu I. Buderi, Daniel Kaniu, Mpho Malima, Sarah Booth, Nadia Fernandes, Pratibha Shah, Chiara Proli, Madeleine Hewish, Sarah Danson, Michael J. Shackcloth, Lily Robinson, Peter Russell, Kevin G. Blyth, Andrew Kidd, Alan Kirk, Mo Asif, Rocco Bilancia, Nikos Kostoulas, Mathew Thomas, Craig Dick, Jason F. Lester, Amrita Bajaj, Apostolos Nakas, Azmina Sodha-Ramdeen, Mohamad Tufail, Molly Scotland, Rebecca Boyles, Sridhar Rathinam, Dean A. Fennell, Claire Wilson, Domenic Marrone, Sean Dulloo, Gurdeep Matharu, Jacqui A. Shaw, Joan Riley, Lindsay Primrose, Ekaterini Boleti, Heather Cheyne, Mohammed Khalil, Shirley Richardson, Tracey Cruickshank, Gillian Price, Keith M. Kerr, Sarah Benafif, Dionysis Papadatos-Pastos, James Wilson, Tanya Ahmad, Jack French, Kayleigh Gilbert, Babu Naidu, Akshay J. Patel, Aya Osman, Christer Lacson, Gerald Langman, Helen Shackleford, Madava Djearaman, Salma Kadiri, Gary Middleton, Angela Leek, Jack Davies Hodgkinson, Nicola Totten, Angeles Montero, Elaine Smith, Eustace Fontaine, Felice Granato, Juliette Novasio, Kendadai Rammohan, Leena Joseph, Paul Bishop, Rajesh Shah, Stuart Moss, Vijay Joshi, Philip Crosbie, Antonio Paiva-Correia, Anshuman Chaturvedi, Lynsey Priest, Pedro Oliveira, Fabio Gomes, Kate Brown, Mathew Carter, Colin R. Lindsay, Fiona H. Blackhall, Matthew G. Krebs, Yvonne Summers, Alexandra Clipson, Jonathan Tugwood, Alastair Kerr, Dominic G. Rothwell, Caroline Dive, Hugo J. W. L. Aerts, Roland F. Schwarz, Tom L. Kaufmann, Peter Van Loo, Gareth A. Wilson, Rachel Rosenthal, Andrew Rowan, Chris Bailey, Claudia Lee, Emma Colliver, Katey S. S. Enfield, Mark S. Hill, Mihaela Angelova, Oriol Pich, Michelle Leung, Alexander M. Frankell, Crispin T. Hiley, Emilia L. Lim, Haoran Zhai, Maise Al Bakir, Nicolai J. Birkbak, Olivia Lucas, Ariana Huebner, Clare Puttick, Kristiana Grigoriadis, Michelle Dietzen, Dhruva Biswas, Foteini Athanasopoulou, Sophia Ward, Jonas Demeulemeester, Carla Castignani, Elizabeth Larose Cadieux, Judit Kisistok, Mateo Sokac, Zoltan Szallasi, Miklos Diossy, Roberto Salgado, Aengus Stewart, Alastair Magness, Clare E. Weeden, Dina Levi, Eva Grönroos, Imran Noorani, Jacki Goldman, Mickael Escudero, Philip Hobson, Roberto Vendramin, Stefan Boeing, Tamara Denner, Vittorio Barbè, Wei-Ting Lu, William Hill, Yutaka Naito, Zoe Ramsden, George Kassiotis, Angela Dwornik, Angeliki Karamani, Benny Chain, David R. Pearce, Despoina Karagianni, Felip Gálvez-Cancino, Georgia Stavrou, Gerasimos Mastrokalos, Helen L. Lowe, Ignacio Garcia Matos, James L. Reading, John A. Hartley, Kayalvizhi Selvaraju, Kezhong Chen, Leah Ensell, Mansi Shah, Maria Litovchenko, Olga Chervova, Piotr Pawlik, Robert E. Hynds, Samuel Gamble, Seng Kuong Anakin Ung, Supreet Kaur Bola, Victoria Spanswick, Yin Wu, Othman Al-Sawaf, Thomas Patrick Jones, Stephan Beck, Miljana Tanic, Teresa Marafioti, Elaine Borg, Mary Falzon, Reena Khiroya, Antonia Toncheva, Christopher Abbosh, Corentin Richard, Cristina Naceur-Lombardelli, Francisco Gimeno-Valiente, Krupa Thakkar, Mariana Werner Sunderland, Monica Sivakumar, Nnennaya Kanu, Paulina Prymas, Sadegh Saghafinia, Sharon Vanloo, Jie Min Lam, Wing Kin Liu, Abigail Bunkum, Sonya Hessey, Simone Zaccaria, Carlos Martínez-Ruiz, James R. M. Black, Kerstin Thol, Robert Bentham, Kevin Litchfield, Nicholas McGranahan, Sergio A. Quezada, Martin D. Forster, Siow Ming Lee, Javier Herrero, Emma Nye, Richard Kevin Stone, Jerome Nicod, Jayant K. Rane, Karl S. Peggs, Kevin W. Ng, Krijn Dijkstra, Matthew R. Huska, Emilie Martinoni Hoogenboom, Fleur Monk, James W. Holding, Junaid Choudhary, Kunal Bhakhri, Marco Scarci, Pat Gorman, Robert C. M. Stephens, Yien Ning Sophia Wong, Zoltan Kaplar, Steve Bandula, Thomas B. K. Watkins, Catarina Veiga, Gary Royle, Charles-Antoine Collins-Fekete, Francesco Fraioli, Paul Ashford, Alexander James Procter, Asia Ahmed, Magali N. Taylor, Arjun Nair, David Lawrence, Davide Patrini, Neal Navani, Ricky M. Thakrar, Charles Swanton, Yinyin Yuan, John Le Quesne, David A. Moore
Journal: Nature Cancer (2024)

Abstract The introduction of the International Association for the Study of Lung Cancer grading system has furthered interest in histopathological grading for risk stratification in lung adenocarcinoma. Complex morphology and high intratumoral heterogeneity present challenges to pathologists, prompting the development of artificial intelligence (AI) methods. Here we developed ANORAK (pyrAmid pooliNg crOss stReam Attention networK), encoding multiresolution inputs with an attention mechanism, to delineate growth patterns from hematoxylin and eosin-stained slides. In 1,372 lung adenocarcinomas across four independent cohorts, AI-based grading was prognostic of disease-free survival, and further assisted pathologists by consistently improving prognostication in stage I tumors. Tumors with discrepant patterns between AI and pathologists had notably higher intratumoral heterogeneity. Furthermore, ANORAK facilitates the morphological and spatial assessment of the acinar pattern, capturing acinus variations with pattern transition. Collectively, our AI method enabled the precision quantification and morphology investigation of growth patterns, reflecting intratumoral histological transitions in lung adenocarcinoma.