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Article History

Received: 14 July 2025

Revised: 12 February 2026

Accepted: 17 March 2026

First Online: 3 April 2026

Competing interests

: M.L. Johnson reports research funding (paid to institution) from AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Boehringer Ingelheim, Calithera Biosciences, Checkpoint Therapeutics, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Lilly, Elicio Therapeutics, EMD Serono, Erasca, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Mirati Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, OncoMed Pharmaceuticals, Pfizer, PMV Pharmaceuticals, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL, and Y-mAbs Therapeutics, and consulting/advisory roles (paid to institution) for AbbVie, Achilles Therapeutics, Amgen, AstraZeneca, Axelia Oncology, Atreca, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Checkpoint Therapeutics, CytomX Therapeutics, Daiichi Sankyo, EcoR1, Editas Medicine, Eisai, EMD Serono, G1 Therapeutics, Genentech/Roche, Genmab, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Ideaya Biosciences, iTeos, Incyte, Janssen, Lilly, Loxo Oncology, Merck, Mirati Therapeutics, Novartis, Oncorus, Pfizer, Regeneron Pharmaceuticals, Ribon Therapeutics, Sanofi-Aventis, Turning Point Therapeutics, and WindMIL. G. Fabbri is an employee of, and reports ownership of stock/shares in, AstraZeneca. C. Ciardullo is an employee of, and reports ownership of stock/shares in, AstraZeneca. J.S. Wang reports honoraria from Regeneron, consulting fees from Fusion, and research funding (paid to institution) from AstraZeneca and several other pharmaceutical companies. G.S. Falchook reports advisory roles (paid to institution) for Fujifilm, Silicon, Navire, Turning Point, Predicine and (paid to self) EMD Serono, honoraria from Total Health Conferencing and Rocky Mountain Oncology Society, research funding (paid to institution) from 3-V Biosciences, Abbisko, AbbVie, ABL Bio ADC Therapeutics, Aileron, American Society of Clinical Oncology, Amgen, ARMO/Eli Lilly, Artios, AstraZeneca, BeiGene, Bioatla, Bioinvent, Biothera, Bicycle, Boehringer Ingelheim, Celldex, Celgene, Ciclomed, Curegenix, Curis, Cyteir, Daiichi, DelMar, eFFECTOR, Eli Lilly, EMD Serono, Epizyme, Erasca, Exelixis, Freenome, Fujifilm, Genmab, GlaxoSmithKline, Hutchison MediPharma, IGM Biosciences, Ignyta, ImmunoGen/MacroGenics, Incyte, Jacobio, Jounce, Kolltan, Loxo/Bayer, MedImmune, Millennium, Merck, miRNA Therapeutics, National Institutes of Health, Navire, NiKang, Novartis, OncoMed, Oncorus, Oncothyreon, Poseida, Precision Oncology, Prelude, PureTech, Pyramid, RasCal, Regeneron, Rgenix, Ribon, Samumed, Sapience, Silicon, Strategia, Syndax, Synthorx/Sanofi, Taiho, Takeda, Tarveda, Teneobio, Tesaro, Tocagen, Turning Point Therapeutics, The University of Texas MD Anderson Cancer Center, Vegenics, and Xencor, royalties from Wolters Kluwer, and travel funding from Bristol Myers Squibb, EMD Serono, Fujifilm, Millennium, and Sarah Cannon Research Institute. S. Jones is an employee of HCA Healthcare and Sarah Cannon Research Institute, and reports ownership of stock/shares in HCA. D. Strickland reports no conflicts. J. Sands reports honoraria from Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Curadev, Daiichi-Sankyo, Fosun, Gilead, Guardant, Jazz Pharmaceutics, Medtronic, Merck, Novartis, Pfizer, Pharma Mar, Sanofi, and Takeda. C.M. Gay reports speaking engagement for AstraZeneca, BeiGene, MJH, OncLive, PeerView, and Targeted Healthcare; advisory board/steering committee membership for AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, G1 therapeutics Jazz Pharmaceuticals, and Monte Rosa Therapeutics; and consulting for Catalyst Pharmaceuticals, Kisoji Biotechnology, and STCube. R.J. Cardnell reports no conflicts of interest. L. Tobalina is an employee of, and reports ownership of stock/shares in, AstraZeneca. S.E. Willis is an employee of, and reports ownership of stock/shares in, AstraZeneca. J. Rodriguez-Canales was previously employed by AstraZeneca and is currently an employee of Daiichi Sankyo. M. Nikolaou is an employee of, and reports ownership of stock/shares in, AstraZeneca. E.V. Jones is an employee of, and reports ownership of stock/shares in, AstraZeneca. S. Schalkwijk was previously employed by AstraZeneca and is currently an employee of, and reports ownership of stock/shares in, GlaxoSmithKline. L. Sainsbury is an employee of, and reports ownership of stock/shares in, AstraZeneca. A. MacDonald is an employee of, and reports ownership of stock/shares in, AstraZeneca. P. Overend is an employee of AstraZeneca and reports ownership of stock/shares in AstraZeneca and GlaxoSmithKline. C. Kennedy is an employee of AstraZeneca, and reports ownership of stock/shares in AstraZeneca, Amgen, and GlaxoSmithKline. J.E. Pease is an employee of, and reports ownership of stock/shares in, AstraZeneca. P. Szekeres is an employee of AstraZeneca and reports ownership of stock/shares in AstraZeneca and Eli Lilly. J. Cosaert is an employee of, and reports ownership of stock/shares in, AstraZeneca. H. Burris III is an employee of, and reports ownership of stock/shares in, HCA Healthcare and Sarah Cannon Research Institute, and reports non-compensated consulting for Daiichi Sankyo, Pfizer, Bayer, GRAIL, Novartis, Vincerx Pharma, AstraZeneca and Incyte, and research grants or funds (paid to institution) from Roche/Genentech, BMS, Incyte, AstraZeneca, Macrogenics, Novartis, Boehringer Ingelheim, Lilly, Seattle Genetics, Merck, Agios, Jounce Therapeutics, Moderna Therapeutics, CytomX, GlaxoSmithKline, Verastem, Tesaro, BioMed Valley Discoveries, TG Therapeutics, Vertex, eFFECTOR Therapeutics, Janssen, Gilead Sciences, BioAtla, CicloMed, Harpoon Therapeutics, Arch, Arvinas, Revolution Medicine, Array BioPharma, Bayer, BIND Therapeutics, Kymab, miRNA Therapeutics, Pfizer, Takeda/Millennium, Foundation Medicine, EMD Serono, ARMO BioSciences, CALGB, Hengrui Therapeutics, Infinity Pharmaceuticals, XBiotech, Zymeworks, Coordination Pharmaceuticals, NGM Biopharmaceuticals, Gossamer Bio, Ryvu Therapeutics, BioTheryX, and AbbVie. L.A. Byers is an employee of The University of Texas MD Anderson Cancer Center, and reports consulting fees from Boehringer Ingelheim, Chugai Pharmaceuticals, AstraZeneca, Genentech, AbbVie, Jazz Pharmaceuticals, Puma Biotechnology, Amgen, Daiichi Sankyo, and Novartis; honoraria from Clinical Care Options and UpToDate; patents royalties and other intellectual property for molecular subtyping of small cell lung cancer to predict therapeutic responses (U.S. Patent No: 11,732,306); methods and systems for diagnosis, classification, and treatment of small cell lung cancer and other high grade neuroendocrine carcinomas; and grants or funds from AstraZeneca, Amgen, and Bristol Myers Squibb.

: The study was performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and are consistent with the International Conference on Harmonisation (ICH)/Good Clinical Practice (GCP) guidelines, applicable regulatory requirements and the AstraZeneca policy on Bioethics and Human Biological Samples. The study protocol and all modifications were approved by relevant ethics committees or institutional review boards: IntegReview, Austin, TX; MD Anderson IRB, Houston, TX; Dana Farber Cancer Institute IRB, Boston, MA; WIRB, Puyallup, WA. It was a requirement for each patient to provide signed and dated informed consent.