@article{2490e9cd872c42e0b9c58d2dce4ac0d6,
title = "A Grading System for Invasive Pulmonary Adenocarcinoma: A Proposal From the International Association for the Study of Lung Cancer Pathology Committee",
abstract = "Introduction: A grading system for pulmonary adenocarcinoma has not been established. The International Association for the Study of Lung Cancer pathology panel evaluated a set of histologic criteria associated with prognosis aimed at establishing a grading system for invasive pulmonary adenocarcinoma. Methods: A multi-institutional study involving multiple cohorts of invasive pulmonary adenocarcinomas was conducted. A cohort of 284 stage I pulmonary adenocarcinomas was used as a training set to identify histologic features associated with patient outcomes (recurrence-free survival [RFS] and overall survival [OS]). Receiver operating characteristic curve analysis was used to select the best model, which was validated (n = 212) and tested (n = 300, including stage I–III) in independent cohorts. Reproducibility of the model was assessed using kappa statistics. Results: The best model (area under the receiver operating characteristic curve [AUC] = 0.749 for RFS and 0.787 for OS) was composed of a combination of predominant plus high-grade histologic pattern with a cutoff of 20% for the latter. The model consists of the following: grade 1, lepidic predominant tumor; grade 2, acinar or papillary predominant tumor, both with no or less than 20% of high-grade patterns; and grade 3, any tumor with 20% or more of high-grade patterns (solid, micropapillary, or complex gland). Similar results were seen in the validation (AUC = 0.732 for RFS and 0.787 for OS) and test cohorts (AUC = 0.690 for RFS and 0.743 for OS), confirming the predictive value of the model. Interobserver reproducibility revealed good agreement (k = 0.617). Conclusions: A grading system based on the predominant and high-grade patterns is practical and prognostic for invasive pulmonary adenocarcinoma.",
keywords = "Adenocarcinoma, Lung, Model, Prognosis, Tumor grading",
author = "Moreira, {Andre L.} and Ocampo, {Paolo S.S.} and Yuhe Xia and Hua Zhong and Russell, {Prudence A.} and Yuko Minami and Cooper, {Wendy A.} and Akihiko Yoshida and Lukas Bubendorf and Mauro Papotti and Giuseppe Pelosi and Fernando Lopez-Rios and Keiko Kunitoki and Dana Ferrari-Light and Sholl, {Lynette M.} and Beasley, {Mary Beth} and Alain Borczuk and Johan Botling and Elisabeth Brambilla and Gang Chen and Chou, {Teh Ying} and Chung, {Jin Haeng} and Sanja Dacic and Deepali Jain and Hirsch, {Fred R.} and David Hwang and Sylvie Lantuejoul and Dongmei Lin and Longshore, {John W.} and Noriko Motoi and Masayuki Noguchi and Claudia Poleri and Natasha Rekhtman and Tsao, {Ming Sound} and Erik Thunnissen and Travis, {William D.} and Yasushi Yatabe and Roden, {Anja C.} and Daigneault, {Jillian B.} and Wistuba, {Ignacio I.} and Kerr, {Keith M.} and Harvey Pass and Nicholson, {Andrew G.} and Mari Mino-Kenudson",
note = "Funding Information: Disclosure: Dr. Beasley reports receiving personal fees from LOXO Oncology and various law firms, outside of the submitted work. Dr. Botling reports receiving personal fees from AstraZeneca, Merck Sharp & Dohme, Roche, Pfizer, Boehringer Ingelheim, Novartis, and Illumina; grants and personal fees from Bristol-Myers Squibb, outside of the submitted work. Dr. Bubendorf reports receiving grants and personal fees from Roche and Merck Sharp & Dohme; personal fees from Bristol-Myers Squibb, Takeda, Bayer, Eli Lilly, Pfizer, and Boehringer Ingelheim, outside of the submitted work. Dr. Dacic reports receiving personal fees from AstraZeneca, Bayer, Takeda, and Bristol-Myers Squibb, outside of the submitted work. Dr. Ferrari-Light reports receiving other compensation for data from Intuitive Surgical Inc., which is outside of and unrelated to the submitted work. Dr. Lopez-Rios reports receiving grants and personal fees from Thermo Fisher , Bristol-Myers Squibb , Roche , Eli Lilly , Pfizer , and Merck Sharp & Dohme ; personal fees from AstraZeneca and Bayer, outside of the submitted work. Dr. Mino-Kenudson reports receiving personal fees from H3 Biomedicine and AstraZeneca; grants from Novartis , outside of the submitted work. Dr. Motoi reports receiving grants and personal fees from Roche Diagnostics and Ono Pharmaceutical; grants from NEC ; personal fees from Bristol-Myers Squibb Japan, Agilent, Cook Japan, Merck Sharp & Dohme, Miraca Life Science, AstraZeneca, Novartis, Chugai, Taiho, Beckton Dickinson Japan, and Covidien Japan, outside of the submitted work. Dr. Nicholson reports receiving personal fees from Merck, Boehringer Ingelheim, Novartis, AstraZeneca, Bristol-Myers Squib, Roche, AbbVie, and Oncologica; grants and personal fees from Pfizer , outside of the submitted work. Dr. Papotti reports receiving personal fees from AstraZeneca, Roche, Pfizer, Merck Sharp & Dohme, AbbVie, and Eli Lilly, outside of the submitted work. Dr. Sholl reports receiving personal fees from LOXO Oncology, AstraZeneca, EMD Serono, and Foghorn Therapeutics; grants from Roche Genentech , outside of the submitted work. Dr. Wistuba reports receiving grants and personal fees from Genentech / Roche , Bayer , Bristol-Myers Squibb , AstraZeneca / Medimmune , Pfizer , HTG Molecular, Asuragen, Merck , and Guardant Health; personal fees from Merck Sharp & Dohme, GlaxoSmithKline, and Oncocyte; grants from Oncoplex, DepArray, Adaptive, Adaptimmune, EMD Serono, Takeda, Amgen, Karus, Johnson & Johnson, Iovance, 4D, Novartis, and Akoya, outside of the submitted work. Dr. Yatabe reports receiving personal fees from Chugai Pharmaceutical, Merck Sharp & Dohme, AstraZeneca, Pfizer, Novartis, Ventana-Roche, Dako-Agilent, and Thermo Fisher Scientific, outside of the submitted work. The remaining authors declare no conflict of interest. Funding Information: This project was supported by grants from the International Association for the Study of Lung Cancer and the National Institutes of Health / National Cancer Institute Early Detection Research Network 1U01CA214195-01 to HP used for biospecimen collection and salary support (DFL). The authors thank the staff of the Center of Biospecimen Research and Development from the New York University for their help in digital pathology and histology for this project. The Center of Biospecimen Research and Development is partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center. Publisher Copyright: {\textcopyright} 2020 International Association for the Study of Lung Cancer",
year = "2020",
month = oct,
doi = "10.1016/j.jtho.2020.06.001",
language = "English (US)",
volume = "15",
pages = "1599--1610",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "10",
}