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

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.