Abstract IA19: New opportunities to the personalization and management of early lung cancer
Authors: James L. Mulshine
Journal: Clinical Cancer Research (2012)

Abstract Lung cancer is the most lethal cancer across the globe with 5-year mortality rates from 80 to over 90% related to the frequency of metastatic disease at initial diagnosis. While metastatic disease is generally incurable, early lung cancer when found still localized to the airways, can frequently be cured. A recent NCI-sponsored, randomized trial of helical CT compared to chest X-ray screening in a high risk cohort reported that the CT arm resulted in a 20% reduction in lung cancer mortality. Coupled with the recent comprehensive revision of lung cancer staging classification, there is a much clearer understanding of the relationship between primary tumor size and lung cancer outcome. The finding that smaller lung cancers are more frequently curable provides a firm conceptual framework for population-based early lung cancer detection strategies as a productive approach to significantly improve lung cancer outcomes. As was demonstrated by reports from both I-ELCAP and the NELSON clinical trials groups, detection rates of stage I lung cancer with helical CT could exceed 70%. Further, the expense and morbidity of invasive diagnostic work-up strategy could be efficient focused based on the suggestion by Yankelevitz and co-workers to use measurement of nodule growth rate on serial CT scans as a biomarker to identify clinically aggressive lung cancers. In this fashion as reported by van Klaveren and co-workers, volumetric determination of suspected lung cancers could enable efficient and accurate lung cancer case detection. The surgical management of early stage lung cancers is increasingly employing video-assisted thoroscopic surgery. Recent studies demonstrate lower complications and more favorable operative mortality rates compared to standard, open thorocotomy approaches. The net effect of these developments is to reduce the possibility of over-treatment in the lung cancer screening setting. These surgical procedures do provide sufficient primary tumor tissue which allows comprehensive molecular analysis of the tumor to identify critical signaling pathways. As the evolution of effective and efficient early lung cancer management unfolds, opportunities exist to better define the relevant at-risk population for screening approaches with the ability to calibrate the frequency of screening relative to the measured risk profile. Information from the imaging and tumor tissue evaluation of detected cases may also provide insight as to the molecular underpinnings of the cancer. This characterization of the primary tumor may subsequently guide the development of more tailored adjuvant therapies and eventually chemopreventive strategies that would be targeted to the specific pathogenic mechanisms of lung carcinogenesis. The continuous improvement of early lung cancer management is an appropriate area to apply the process improvement strategies proposed by the Institute of Medicine in their Learning Health System approach. In this way, the component elements of the screening process can be optimized and personalized to allow overall progress in advancing public health benefit with CT-based lung cancer screening.