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BACKGROUND: A paucity of strategies exist for extensive-stage small cell lung cancer (ES-SCLC) patients who fail the first-line chemotherapy. Apatinib is a tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor receptor-2 (VEGFR-2), which has been demonstrated to have active anti-tumor activity in ES-SCLC when used only or combined with PD-1 inhibitors or chemotherapy with good tolerance. However, the efficacy and safety of apatinib monotherapy is unclear in second-line or beyond treatment of ES-SCLC. METHODS: In this prospective, exploratory, single-arm, multi-center study, eligible patients were aged 18 years or older with histologically confirmed ES-SCLC, and had progressed on, or were intolerant to previous systemic treatment. Patients received apatinib 500 mg (orally qd, every 4 weeks a cycle). The efficacy was assessed after 1 cycle and then every 2 cycles based on computed tomography imaging per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). The primary endpoint was progression-free survival (PFS). The adverse events (AEs) were assessed per the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 (NCI-CTCAE 4.0). This study is registered in the Chinese Clinical Trial Registry, number ChiCTR-OPC-17013964. RESULTS: From 28 July 2017 to 21 June 2019, 62 patients were screened for eligibility, among whom 57 patients were available for efficacy and safety analysis. The objective response rate (ORR) was 14.3% and disease control rate (DCR) was 79.6%. The median PFS was 5.6 months [95% confidence interval (CI): 3.3–8.0 months] and the median overall survival (OS) was 11.2 months (95% CI: 7.5–24.0 months). Among the participants who received apatinib as second-line treatment, the median PFS and OS were 6.1 months (95% CI: 2.6–7.6 months) and 12.0 months (95% CI: 7.9 months to not reached), respectively. The most common AEs of all grades were anemia (36.8%), hypertension (33.3%), fatigue (31.6%), blood bilirubin increased (22.8%), elevated transaminase (19.3%), and hand-foot syndrome (17.54%). Grade 3 AEs included 2 (3.5%) cases of hypertension and 1 (1.8%) case of fatigue. No grade 4/5 AEs were observed. CONCLUSIONS: Apatinib showed encouraging anti-tumor activity in pretreated ES-SCLC patients with tolerable toxicities. Further larger scale studies are warranted to demonstrate the efficacy of apatinib.

Since the introduction of economic reforms in the late 1970s, China has experienced phenomenal economic growth along with rapid urbanization. The accelerated urbanization coincides with remarkable social-economic transformations and urban landscape changes. A city, as an urban system, is composed of social and physical subsystems that interact with each other. Equally assessing each component is necessary for a comprehensive understanding of the urbanization process. The goal of this thesis research is to deconstruct the urbanization process through a social-ecological perspective. More specifically, this study examines social transformations, physical evolutions, and their relationships. Four research questions are proposed as (1) How does urban social landscape transform in time and space? (2) What trends are apparent in the urban land growth process and spatial heterogeneity? (3) How does social transformation relate to urban land growth, within a spatio-temporal perspective? and (4) How do social-demographic features relate to residents’ use and perception of urban green open spaces, focusing on the ecological services provided by and the need to improve those spaces? Given the lack of research on second-tier cities’ growth processes, this study selects Wuhan, a megacity in central China, as a case study, with a focus on its urban development zone (UDZ). A social-ecological approach is applied to study the multi-dimensional features of an urban system. The thesis is in paper format, containing five chapters. Besides the Introduction (Chapter 1) and Conclusion (Chapter 5), the main body consists of three articles. These three articles correspond to the four research questions proposed. Chapter 2 responds to the first research question by addressing how the urban social landscape transforms. Chapter 3 seeks to answer the second and third questions by evaluating urban land growth and its links with social factors from a spatio-temporal perspective. Chapter 4 matches the fourth question by seeking to understand residents’ preferences and feelings toward the urban green open space. Chapter 1 introduces the research context, reviews the urban ecology theory and relevant empirical research, as well as assesses the social-ecological approach related to studying the urban system. In this chapter, we also propose an improved social-ecological system (ISES) framework which guides the equally weighted study of both social and physical subsystems in an urban area. Chapter 2 (the first paper) seeks to investigate progressive transformations in the social dimensions of Wuhan UDZ while also focusing on their spatial transformations, using national census data in 1990, 2000, and 2010. We used varimax rotated principal component analysis (PCA) for the extraction of social dimensions and ArcMap for spatial visualization. This allows us to further analyze the spatial distribution of social clusters. The results suggest that industrial relocation, educational attainment increase, population aging, and migration are the main characteristics of social transformation during 1990 and 2010. Industrial relocation along with the spatial separation appeared as principal social dimensions in the 1990s but became more prominent in the 2000s, accompanied by the improvement of workers’ education levels. Aging population presented spatial movement outward from the city center. Population mobility increased significantly, and immigration became an important social dimension and presented spatial expansion in the 2000s. The socio-spatial patterns transform with a combination of concentric rings and sectoral clusters in different stages. These transformations are formed by the regional push-pull forces and the centripetal-centrifugal forces inside the city. We conclude that the social landscape transforms in a way with diversity and inclusion. Government dominates socio-spatial transformations in the initial stages, while market plays an increasing role in the later stages. To build a more inclusive society requires continuous and systematic improvement of relevant policies. Chapter 3 (the second paper) discusses urban land growth patterns and answers how social factors are associated with the evolution patterns between 1990 and 2010. We extract land cover information based on Landsat images with the vegetation area – impervious surface –water area (V-I-W) model and examine the urban growth patterns during various stages using landscape metrics of the area, aggregation, and shape. Then, we apply geographically weighted regression (GWR) to depict the link between urban land metrics and social factors. The results show that urban land coalescence and diffusion simultaneously exist; the city center is dominated by redevelopment, infilling, edge expansion; and the peripheral areas by outlying expansion. GWR coefficient surfaces show little differences in the models between social factors and urban land area metrics PLAND while remarkable differences are present in the coefficients of GWR models for the urban land patch shape irregularities and social factors. Urban land growth patterns relate to the government-led land supply system, the functional zoning of urban space planning, and the agglomeration and dispersion of social space under the market orientation. The authors conclude that urban management should consider the coexistence of different spatial growth modes and introduce factors such as social preferences in the urban land layout. This may apply to rapidly urbanizing areas. Chapter 4 (the third paper) aims to understand social-natural relationships, with a focus on how socio-demographic features can shape residents’ preference toward green open spaces and their perceptions of ecological services and improvements. Data is collected through online questionnaire surveys and interviews. The results indicate that preferences toward green open spaces vary among different social groups. Demands for improvement to green open spaces are rooted in residents’ appreciation for daily relaxation and health benefits, and link with their preference for visiting. However, how residents perceive green open spaces’ benefits does not rely only on an in-person visit. Interaction experience with nature and knowledge of natural development affect perception of daily use and health-related services. Residents’ perceptions of green open space’s ecological functions are associated with the changes in nature reported by those respondents. Responses to improving green open space reflect the residents’ pursuit of the aesthetics and practicality of such spaces. Though respondents are commonly aware of the ecological importance of green open space, there are differences in their willingness to voluntarily participate in its management. We conclude that to encourage the public to participate in configuration and improvement of green open spaces through a variety of ways, including considering residents’ opinions, is an efficient way in order to better social-ecological relationships. Chapter 5 reviews the main findings and conclusions, research limitations as well as future possibilities. This study establishes a dialogue between urban social and physical subsystems, with an integrated quantitative study of the urbanization process, emphasizing the relationships between two urban subsystems. It provides a comprehensive social-ecological view on a second-tier city based on the social and physical transformations that occurred in Wuhan during a transitional period of a socialist market economy. We conclude that the development of China's second-tier cities between 1990 and 2010 is characterized by the transformations of social dimensions and landscape, the coexistence of multiple urban spatial development modes, and the spatial differentiation between the center and the periphery of the city. The GWR models present spatial non-stationary relationships between social factors and the urban patch shape regularities. The further examination of social-natural relationships finds that residents’ social-demographic features and environmental experience affect their perceptions toward green open space, especially ecological services and improvement necessity. The evolution of urban social and physical systems and their relationships has brought increased attention to inclusive urban social management, public participatory planning, and people-centered social and ecological interactions. This research provides a constructive rethinking of second-tier cities’ growth in China and may serve as a reference for other rapidly urbanizing areas.