• Bo Liu, Wenhao Chi, Xinran Li, Peng Li, Wenhua Liang, Haiping Liu, Wei Wang, and Jianxing He.
• Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China. bliu@amss.ac.cn.
• J. Cancer Res. Clin. Oncol. 2020 Jan 1; 146 (1): 153-185.

PurposeLung cancer is the commonest cause of cancer deaths worldwide, and its mortality can be reduced significantly by performing early diagnosis and screening. Since the 1960s, driven by the pressing needs to accurately and effectively interpret the massive volume of chest images generated daily, computer-assisted diagnosis of pulmonary nodule has opened up new opportunities to relax the limitation from physicians' subjectivity, experiences and fatigue. And the fair access to the reliable and affordable computer-assisted diagnosis will fight the inequalities in incidence and mortality between populations. It has been witnessed that significant and remarkable advances have been achieved since the 1980s, and consistent endeavors have been exerted to deal with the grand challenges on how to accurately detect the pulmonary nodules with high sensitivity at low false-positive rate as well as on how to precisely differentiate between benign and malignant nodules. There is a lack of comprehensive examination of the techniques' development which is evolving the pulmonary nodules diagnosis from classical approaches to machine learning-assisted decision support. The main goal of this investigation is to provide a comprehensive state-of-the-art review of the computer-assisted nodules detection and benign-malignant classification techniques developed over three decades, which have evolved from the complicated ad hoc analysis pipeline of conventional approaches to the simplified seamlessly integrated deep learning techniques. This review also identifies challenges and highlights opportunities for future work in learning models, learning algorithms and enhancement schemes for bridging current state to future prospect and satisfying future demand.ConclusionIt is the first literature review of the past 30 years' development in computer-assisted diagnosis of lung nodules. The challenges indentified and the research opportunities highlighted in this survey are significant for bridging current state to future prospect and satisfying future demand. The values of multifaceted driving forces and multidisciplinary researches are acknowledged that will make the computer-assisted diagnosis of pulmonary nodules enter into the main stream of clinical medicine and raise the state-of-the-art clinical applications as well as increase both welfares of physicians and patients. We firmly hold the vision that fair access to the reliable, faithful, and affordable computer-assisted diagnosis for early cancer diagnosis would fight the inequalities in incidence and mortality between populations, and save more lives.

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