Beatrice Aramini1, Christian Casali2, Alessandro Stefani2, Stefania Bettelli3, Susanne Wagner4, Zaina Sangale4, Elisha Hughes4, Jerry S Lanchbury4, Antonino Maiorana3, Uliano Morandi2. 1. Department of Medical and Surgical Sciences for Children and Adults, Operative Unit of Thoracic Surgery, University of Modena and Reggio Emilia, Via Largo del Pozzo 71- 41124, Modena, Italy. Electronic address: beatrice.aramini@gmail.com. 2. Department of Medical and Surgical Sciences for Children and Adults, Operative Unit of Thoracic Surgery, University of Modena and Reggio Emilia, Via Largo del Pozzo 71- 41124, Modena, Italy. 3. Department of Diagnostic and Clinical Medicine and Public Health, Operative Unit of Pathologic Anatomy, University of Modena and Reggio Emilia, Via Largo del Pozzo 71- 41124, Modena, Italy. 4. Myriad Genetics Inc., Salt Lake City, 84108 UT, USA.
Abstract
OBJECTIVES: Optimal procedures for adjuvant treatment and post-surgical surveillance of resected non-small-cell lung cancer remain under discussion. Pathological features are the main determinant of follow-up therapy but have limited ability to identify patients at risk of recurrence. Increasingly, molecular markers are incorporated into clinical decision-making, including measures of tumor growth. The CCP score is a quantitative, molecular measure of proliferation derived from the RNA expression of 31 cell cycle genes and a component of the molecular prognostic score (mPS). The mPS score is a linear combination of CCP score and pathological stage. CCP score and mPS are independent predictors of survival in resected lung adenocarcinoma. MATERIALS AND METHODS: CCP scores were determined by RT-qPCR for 318 patients diagnosed with stage I-II lung adenocarcinoma. Association of mPS and CCP score with distant recurrence and lung-cancer specific survival was assessed in Cox proportional hazards regression models adjusted for age, gender, tumor size, pathological stage and pleural invasion. Distant recurrence-free survival and lung-cancer specific survival by mPS risk group were calculated by Kaplan-Meier survival analysis. RESULTS: CCP scores were obtained for 205 stage I and 84 stage II patients. CCP score and mPS were independent markers of distant recurrence (CCP: HR 1.62, 95%CI 1.15-2.29, p=0.0055; mPS: HR 2.22, 95%CI 1.11-4.44, p=0.023). Patients with low mPS tumors were at significantly reduced risk of distant recurrence (log-rank p=4.2×10-5). Among stage I patients, stratification by mPS identified a patient group with increased risk of distant recurrence (36%, 95%CI 28-46%, log-rank p=0.0011) CONCLUSIONS: The molecular prognostic score stratifies early-stage, resected lung cancer patients for risk of distant recurrence and could be useful to inform treatment and surveillance decisions.
OBJECTIVES: Optimal procedures for adjuvant treatment and post-surgical surveillance of resected non-small-cell lung cancer remain under discussion. Pathological features are the main determinant of follow-up therapy but have limited ability to identify patients at risk of recurrence. Increasingly, molecular markers are incorporated into clinical decision-making, including measures of tumor growth. The CCP score is a quantitative, molecular measure of proliferation derived from the RNA expression of 31 cell cycle genes and a component of the molecular prognostic score (mPS). The mPS score is a linear combination of CCP score and pathological stage. CCP score and mPS are independent predictors of survival in resected lung adenocarcinoma. MATERIALS AND METHODS: CCP scores were determined by RT-qPCR for 318 patients diagnosed with stage I-II lung adenocarcinoma. Association of mPS and CCP score with distant recurrence and lung-cancer specific survival was assessed in Cox proportional hazards regression models adjusted for age, gender, tumor size, pathological stage and pleural invasion. Distant recurrence-free survival and lung-cancer specific survival by mPS risk group were calculated by Kaplan-Meier survival analysis. RESULTS: CCP scores were obtained for 205 stage I and 84 stage II patients. CCP score and mPS were independent markers of distant recurrence (CCP: HR 1.62, 95%CI 1.15-2.29, p=0.0055; mPS: HR 2.22, 95%CI 1.11-4.44, p=0.023). Patients with low mPS tumors were at significantly reduced risk of distant recurrence (log-rank p=4.2×10-5). Among stage I patients, stratification by mPS identified a patient group with increased risk of distant recurrence (36%, 95%CI 28-46%, log-rank p=0.0011) CONCLUSIONS: The molecular prognostic score stratifies early-stage, resected lung cancerpatients for risk of distant recurrence and could be useful to inform treatment and surveillance decisions.
Authors: Andre L Moreira; Paolo S S Ocampo; Yuhe Xia; Hua Zhong; Prudence A Russell; Yuko Minami; Wendy A Cooper; Akihiko Yoshida; Lukas Bubendorf; Mauro Papotti; Giuseppe Pelosi; Fernando Lopez-Rios; Keiko Kunitoki; Dana Ferrari-Light; Lynette M Sholl; Mary Beth Beasley; Alain Borczuk; Johan Botling; Elisabeth Brambilla; Gang Chen; Teh-Ying Chou; Jin-Haeng Chung; Sanja Dacic; Deepali Jain; Fred R Hirsch; David Hwang; Sylvie Lantuejoul; Dongmei Lin; John W Longshore; Noriko Motoi; Masayuki Noguchi; Claudia Poleri; Natasha Rekhtman; Ming-Sound Tsao; Erik Thunnissen; William D Travis; Yasushi Yatabe; Anja C Roden; Jillian B Daigneault; Ignacio I Wistuba; Keith M Kerr; Harvey Pass; Andrew G Nicholson; Mari Mino-Kenudson Journal: J Thorac Oncol Date: 2020-06-17 Impact factor: 15.609