Defining Local-regional Control and Its Importance in Locally Advanced Non-small Cell Lung Carcinoma: An RTOG Analysis

• Authors: Mitchell Machtay, University Hospitals/Seidman Cancer Center and Case Western Reserve University; Rebecca Paulus, American College of Radiology; Jennifer Moughan, American College of Radiology; Ritsuko Komaki, University of Texas MD Anderson Cancer Center; Jeffrey Bradley, Washington University; Hak Choy, University of Texas at Dallas; Kathy Albain, Loyola University; Benjamin Movsas, Henry Ford Hospital; William T. Sause, University of Utah; Walter J Curran, Emory University
• Journal Title: Journal of Thoracic Oncology
• Volume: Volume 7, Number 4
• Publisher: Elsevier: 12 months | 2012-04-01, Pages 716-722
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1097/JTO.0b013e3182429682
• Subjects: Health Sciences, Oncology; Health Sciences, Radiology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Respiratory System; Non-small cell lung cancer; Local control; Chemoradiotherapy; POSITRON-EMISSION-TOMOGRAPHY; PHASE-III TRIAL; CONCURRENT CHEMORADIATION; COMBINED CHEMOTHERAPY; RANDOMIZED-TRIAL; CANCER; RADIOTHERAPY; CHEMORADIOTHERAPY; IRRADIATION; PET

Abstract

INTRODUCTION: Local-regional control (LRC) rates for non-small cell lung cancer after chemoradiotherapy were studied (using two different definitions of LRC) for the association between LRC and survival. METHODS:: Seven legacy Radiation Therapy Ooncology Group trials of chemoradiotherapy for locally advanced non-small cell lung cancer were analyzed. Two different definitions of LRC were studied: (1) freedom from local progression (FFLP-LRC), the traditional Radiation Therapy Oncology Group methodology, in which a failure is intrathoracic tumor progression by World Health Oorganization criteria; and (2) response-mandatory (strict-LRC), in which any patient not achieving at least partial response was considered to have failure at day 0. Testing for associations between LRC and survival was performed using a Cox multivariate model that included other potential predictive factors. RESULTS:: A total of 1390 patients were analyzed. The LRC rate at 3 years was 38% based on the FFLP-LRC definition and 14% based on the strict-LRC definition. Performance status, concurrent chemotherapy, and radiotherapy dose intensity (biologically equivalent dose) were associated with better LRC (using either definition). With the strict-LRC definition (but not FFLP-LRC), age was also important. There was a powerful association between LRC and overall survival (p, 0.0001) on univariate and multivariate analyses. Age, performance status, chemotherapy sequencing, and biologically equivalent dose were also significantly associated with survival. Histology and gender were also significant if the strict-LRC model was used. CONCLUSIONS:: LRC is associated with survival. The definition of LRC affects the results of these analyses. A consensus definition of LRC, incorporating functional imaging and/or central review, is needed, with the possibility of using LRC as a surrogate end point in future trials.