Prediction of distant recurrence in resected stage I and II lung adenocarcinoma

Beatrice Aramini; Christian Casali; Alessandro Stefani; Stefania Bettelli; Susanne Wagner; Zaina Sangale; Elisha Hughes; Jerry S Lanchbury; Antonino Maiorana; Uliano Morandi

doi:10.1016/j.lungcan.2016.09.005

Prediction of distant recurrence in resected stage I and II lung adenocarcinoma

Lung Cancer. 2016 Nov:101:82-87. doi: 10.1016/j.lungcan.2016.09.005. Epub 2016 Sep 6.

Affiliations

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: [email protected].
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.

PMID: 27794412
DOI: 10.1016/j.lungcan.2016.09.005

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.

Keywords: Biomarkers; Lung adenocarcinoma; Post-surgical treatment; Prognosis; Surveillance.

MeSH terms

Adenocarcinoma / metabolism
Adenocarcinoma / pathology
Adenocarcinoma / surgery*
Adenocarcinoma of Lung
Aged
Biomarkers
Carcinoma, Non-Small-Cell Lung / metabolism
Carcinoma, Non-Small-Cell Lung / pathology
Carcinoma, Non-Small-Cell Lung / surgery*
Clinical Decision-Making
Female
Humans
Lung Neoplasms / metabolism
Lung Neoplasms / pathology
Lung Neoplasms / surgery*
Male
Middle Aged
Neoplasm Recurrence, Local / metabolism
Neoplasm Recurrence, Local / pathology*
Neoplasm Staging
Predictive Value of Tests*
Prognosis
Risk

Substances

Biomarkers