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Retrofitting microhabitat features is a common ecological engineering technique for enhancing biodiversity and abundance of small, epilithic organisms on artificial shorelines by providing refuge spaces and/or ameliorating abiotic conditions. These features are typically too small to be utilised as refugia by larger, highly motile consumers such as fish, but they may affect these organisms through other mechanisms. This study sought to determine whether microhabitat enhancement units alter the fish abundance, richness and assemblage composition on tropical seawalls and explores possible underlying trophic mechanisms. We created 12 experimental plots consisting of 6 enhanced plots, each with 20 microhabitat enhancement tiles, and 6 control plots without tiles on intertidal seawalls at Pulau Hantu, an offshore island south of mainland Singapore. Benthic cover and fish assemblage were surveyed within each plot using photoquadrats and underwater video cameras, respectively, from April 2018 to February 2019. We found greater abundance and species richness and distinct assemblages of fish in the enhanced plots compared to the control plots. These differences were driven largely by an increase in both abundance and richness of fish species with epibenthic-feeding strategies and were significantly associated with higher biotic cover in the enhanced plots, especially epilithic algal matrix (EAM). Our results indicate that, in addition to facilitating epilithic organisms, microhabitat enhancement can provide food resources for epibenthic-feeding fishes, increase fish biodiversity, and alter fish assemblages in tropical urbanised shorelines.

Concrete is one of the most commonly used materials in the construction of coastal and marine infrastructure despite the well known environmental impacts which include a high carbon footprint and high alkalinity (~pH 13). There is an ongoing discussion regarding the potential positive effects of lowered concrete pH on benthic biodiversity, but this has not been investigated rigorously. Here, we designed a manipulative field experiment to test whether carbonated (lowered pH) concrete substrates support greater species richness and abundance, and/or alter community composition, in both temperate and tropical intertidal habitats. We constructed 192 experimental concrete tiles, half of which were carbonated to a lower surface pH of 7-8 (vs. control pH of >9), and affixed them to seawalls in the United Kingdom and Singapore. There were 2 sites per country, and 6 replicate tiles of each treatment were collected at 4 time points over a year. Overall, we found no significant effect of lowered pH on the abundance, richness, or community assemblage in both countries. Separate site- and month-specific generalised linear models (GLMs) showed only sporadic effects: i.e. lowered pH tiles had a small positive effect on early benthic colonisation in the tropics but this was later succeeded by similar species assemblages regardless of treatment. Thus, while it is worth considering the modification of concrete from an environmental/emissions standpoint, lowered pH may not be a suitable technique for enhancing biodiversity in the marine built environment.

The sprawl of marine construction is one of the most extreme human modifications to global seascapes. Nevertheless, its global extent remains largely unquantified compared to that on land. We synthesized disparate information from a diversity of sources to provide a global assessment of the extent of existing and projected marine construction and its effects on the seascape. Here we estimated that the physical footprint of built structures was at least 32,000 km2 worldwide as of 2018, and is expected to cover 39,400 km2 by 2028. The area of seascape modified around structures was 1.0–3.4 × 106 km2 in 2018 and was projected to increase by 50–70% for power and aquaculture infrastructure, cables and tunnels by 2028. In 2018, marine construction affected 1.5% (0.7–2.4%) of global Exclusive Economic Zones, comparable to the global extent of urban land estimated at 0.02–1.7%. This study provides a critical baseline for tracking future marine human development.

Coral reefs worldwide are facing multiple severe stressors leading to ecosystem degradation, but local extinctions of species are not well documented. Here, we track the diversity of Pocilloporidae Gray, 1840 coral species—many of which are known to be sensitive to environmental disturbances—on Singapore reefs through time, integrating information from taxonomically verified museum specimens, careful examination of the literature, and DNA sequences. We found that more Pocilloporidae species were detected in the past than at present. A total of five species were historically recorded under Pocillopora Lamarck, 1816; Seriatopora Lamarck, 1816; and Stylophora Schweigger, 1820. Among the five species, only Pocillopora acuta Lamarck, 1816 appears to remain on Singapore reefs. The absence of Seriatopora for over half a century and the recent losses of Stylophora and the other species of Pocillopora are likely caused by habitat loss and other stressors associated with coastal urbanization, which have been further exacerbated by recent bleaching events.

Artificial structures are agents of change in marine ecosystems. They add novel habitat for hard-substrate organisms and modify the surrounding environment. Most research to date has focused on the communities living directly on artificial structures, and more research is needed on the potential impacts these structures have on nearby communities and the surrounding environment. We compared the sedimentary habitat surrounding two types of artificial structures (pilings and seawalls) to sediments adjacent to rocky reefs using a combination of traditional sediment analyses, stable isotope analysis, and environmental DNA. Artificial and natural shore sediments were best differentiated by sediment variables strongly associated with flow speed. Pilings sediments had significantly finer grain size, higher organic content, and generally lower C:N ratios than sediments adjacent to the other habitat types, suggesting flow is reduced by pilings. Sedimentary assemblages near pilings were also consistent with those predicted under low-flow conditions, with elevated bacterial colonization and increased relative abundances of small deposit feeders compared with other habitat types. Additionally, lumbrinerid polychaetes in pilings sediments had reduced δ15N values, suggesting different detrital resources and fewer trophic linkages compared with lumbrinerids in other habitats. Woody detritus was greater adjacent to seawalls than to natural rocky shores or pilings. Our findings suggest that artificial structures have the potential to influence adjacent soft sediments through changes to sediment properties that affect infaunal and microbial communities, as well as trophic linkages for some consumers. We hypothesize that this is due to a combination of altered flow, differing detrital subsidies, and differing adjacent land-use among habitat types. Managers should consider the potential for changed sediment properties and ecology when deciding where to build different types of artificial structures. Further manipulative experiments are needed to understand mechanisms of change and help manage the impacts of artificial structures on the seafloor.

Adaptation to sea level rise (SLR) is primarily taking place at the local level, with varied governments grappling with the diverse ways that SLR will affect cities. Interpreting SLR in the context of local planning requires integrating knowledge across many disciplines, and expert knowledge can help planners understand the potential ramifications of decisions. Little research has focused on the role that experts play in local adaptation planning. Understanding how and when local governments undertake adaptation planning, and how scientists and scientific information can be effectively incorporated into the planning process, is vital to guide scientists who wish to engage in the planning process. This study aimed to establish how experts are currently involved in SLR planning, identify any gaps between planners’ needs and expert involvement, and determine the characteristics of experts that are perceived as highly valuable to the planning process. We surveyed individuals involved with planning in a broad range of US coastal communities about SLR planning and the role that experts have played in the process. We found that SLR planning is widespread in cities across geographic regions, population sizes, and population characteristics and has increased rapidly since 2012. Contrary to our expectation, whether a SLR plan existed for each city was not related to the percentage of the population living on vulnerable lands or the property value of those lands. Almost all cities that have engaged in SLR planning involved experts in that process. Planners identify atmospheric scientists, oceanographers, economists and political scientists, and geologists as currently underutilized according to planners’ needs. Members of these expert disciplines, when involved in planning, were also unlikely to be affiliated with the local planning government, but rather came from other governmental and academic institutions. Highly effective experts were identified as making scientific research more accessible and bringing relevant research to the attention of planners. Results from our dataset suggest that planners perceive local SLR planning could benefit from increased involvement of experts, particularly atmospheric scientists, oceanographers, economists and political scientists, and geologists. Since experts in these disciplines were often not affiliated with local governments, increasing the exchange of information between local governments and academic and other (non-local) government organizations could help draw valued experts into the planning process.

Macrophyte detritus from exogenous sources can play an important role in structuring benthic communities. Macrofaunal responses to seagrass wrack, mangrove leaf litter, and detritus from brown and green macroalgae have previously been examined through enrichment experiments. Yet effects from red macroalgal detritus, which is a major component of algal drift in many regions, are not well understood. In this study, enrichment experiments were performed on a shallow subtidal sandflat in Puget Sound, Washington, USA with detritus from three species of red macroalgae to assess: (1) whether macrofaunal assemblages were affected by two different “dosages” of red macroalgal enrichment (100 ml vs 500 ml per 0.079 m3 of sediment); (2) whether macrofaunal response differed between one-time and repeated (weekly) additions of red macroalgae; and (3) whether responses to red macroalgal enrichment changed over time. There appeared to be little or no effect on macrofauna from one-time enrichment regardless of the amount/dosage of algae added. However, weekly additions of red macroalgae led to negative responses across macrofaunal taxa. These responses occurred rapidly, within the first 3 weeks, and were largely unchanged after 7 weeks, intensifying for only 2 of the 10 most common taxa. No opportunistic responses to weekly additions were observed. Frequent influx of some types of red macroalgae may degrade the quality of sedimentary habitats by leaching chemically defensive compounds or through other mechanisms, which should be investigated in future studies. Although weekly enrichment treatments were informed by previous estimates of detrital delivery rates near hard-bottom habitats in the same locality, further research is needed to assess detrital influx frequency and community response in other regions where red macroalgal detritus is common, and to understand the broader implications of exogenous detritus from red macroalgae on benthic ecosystems.

Urbanization is a process that heavily alters marine and terrestrial environments, though terrestrial urban ecosystems have been studied far more intensively. Terrestrial studies suggest that urbanization can facilitate mesopredators by enhancing food and shelter resources and reducing predation pressure from apex consumers. This in turn has considerable consequences for ecological communities. We evaluated spatial distribution patterns and habitat-use of the marine mesopredator, giant Pacific octopus (Enteroctopus dofleini), relative to terrestrial urbanization intensity in Puget Sound, Washington, USA. Using field surveys and citizen-contributed data for E. dofleini, we examined whether: (1) Distribution was related to urbanization, (2) Abundance was related to the extent of benthic anthropogenic debris, and (3) Diet differed as a function of urbanization and den cover. Our results suggest that urbanization impacts may differ with depth. Mixed-effects logistic regression model estimates for the probability of occurrence increased with urbanization in deep-water (> 24 m), and decreased with urbanization in shallow water (< 18 m). Accompanying field surveys indicated that E. dofleini abundance was correlated with the number of benthic anthropogenic debris items, and that E. dofleini diets were not affected by urbanization intensity or den cover. Though E. dofleini may be synanthropic within certain urban environments, the mechanisms driving this pattern likely differ from those affecting common urban mesopredators on land, with den provisioning from man-made structures being more important than altered food resources.

Marine urbanisation often results in the proliferation of artificial coastal defences and heavy sedimentation, adversely impacting coral reef systems in tropical coastal cities. Knowledge of how motile organisms, such as reef fish, respond to novel human-made habitats and high sedimentation is limited. Here, we examine the role of sloping granite seawalls in supporting reef fishes that utilise the epilithic algal matrix (EAM) as a food resource. We surveyed fish assemblages and feeding activities on seawalls and reef flats, and conducted a field experiment to examine the effects of sediment on EAM feeding rates. Seawalls and reef flats supported distinct fish assemblage composition with significantly greater feeding activity on seawalls. However, reduced feeding activity on EAM with elevated sediment loads suggests that urban sedimentation may limit the utility of this novel feeding ground for nearshore communities. These findings illustrate the complexities and interactive effects of anthropogenic changes driven by coastal urbanisation.

Extensive development and construction in marine and coastal systems is driving a phenomenon known as “ocean sprawl”. Ocean sprawl removes or transforms marine habitats through the addition of artificial structures and some of the most significant impacts are occurring in sedimentary environments. Marine sediments have substantial social, ecological, and economic value, as they are rich in biodiversity, crucial to fisheries productivity, and major sites of nutrient transformation. Yet the impact of ocean sprawl on sedimentary environments has largely been ignored. Here we review current knowledge of the impacts to sedimentary ecosystems arising from artificial structures.\ud \ud Artificial structures alter the composition and abundance of a wide variety of sediment-dependent taxa, including microbes, invertebrates, and benthic-feeding fishes. The effects vary by structure design and configuration, as well as the physical, chemical, and biological characteristics of the environment in which structures are placed. The mechanisms driving effects from artificial structures include placement loss, habitat degradation, modification of sound and light conditions, hydrodynamic changes, organic enrichment and material fluxes, contamination, and altered biotic interactions. Most studies have inferred mechanism based on descriptive work, comparing biological and physical processes at various distances from structures. Further experimental studies are needed to identify the relative importance of multiple mechanisms and to demonstrate causal relationships. Additionally, past studies have focused on impacts at a relatively small scale, and independently of other development that is occurring. There is need to quantify large-scale and cumulative effects on sedimentary ecosystems as artificial structures proliferate. We highlight the importance for comprehensive monitoring using robust survey designs and outline research strategies needed to understand, value, and protect marine sedimentary ecosystems in the face of a rapidly changing environment.

Human population density within 100 km of the sea is approximately three times higher than the global average. People in this zone are concentrated in coastal cities that are hubs for transport and trade - which transform the marine environment. Here, we review the impacts of three interacting drivers of marine urbanization (resource exploitation, pollution pathways and ocean sprawl) and discuss key characteristics that are symptomatic of urban marine ecosystems. Current evidence suggests these systems comprise spatially heterogeneous mosaics with respect to artificial structures, pollutants and community composition, while also undergoing biotic homogenization over time. Urban marine ecosystem dynamics are often influenced by several commonly observed patterns and processes, including the loss of foundation species, changes in biodiversity and productivity, and the establishment of ruderal species, synanthropes and novel assemblages. We discuss potential urban acclimatization and adaptation among marine taxa, interactive effects of climate change and marine urbanization, and ecological engineering strategies for enhancing urban marine ecosystems. By assimilating research findings across disparate disciplines, we aim to build the groundwork for urban marine ecology - a nascent field; we also discuss research challenges and future directions for this new field as it advances and matures. Ultimately, all sides of coastal city design: architecture, urban planning and civil and municipal engineering, will need to prioritize the marine environment if negative effects of urbanization are to be minimized. In particular, planning strategies that account for the interactive effects of urban drivers and accommodate complex system dynamics could enhance the ecological and human functions of future urban marine ecosystems.

Human population growth and accelerating coastal development have been the drivers for unprecedented construction of artificial structures along shorelines globally. Construction has been recently amplified by societal responses to reduce flood and erosion risks from rising sea levels and more extreme storms resulting from climate change. Such structures, leading to highly modified shorelines, deliver societal benefits, but they also create significant socioeconomic and environmental challenges. The planning, design and deployment of these coastal structures should aim to provide multiple goals through the application of ecoengineering to shoreline development. Such developments should be designed and built with the overarching objective of reducing negative impacts on nature, using hard, soft and hybrid ecological engineering approaches. The design of ecologically sensitive shorelines should be context-dependent and combine engineering, environmental and socioeconomic considerations. The costs and benefits of ecoengineered shoreline design options should be considered across all three of these disciplinary domains when setting objectives, informing plans for their subsequent maintenance and management and ultimately monitoring and evaluating their success. To date, successful ecoengineered shoreline projects have engaged with multiple stakeholders (e.g. architects, engineers, ecologists, coastal/port managers and the general public) during their conception and construction, but few have evaluated engineering, ecological and socioeconomic outcomes in a comprehensive manner. Increasing global awareness of climate change impacts (increased frequency or magnitude of extreme weather events and sea level rise), coupled with future predictions for coastal development (due to population growth leading to urban development and renewal, land reclamation and establishment of renewable energy infrastructure in the sea) will increase the demand for adaptive techniques to protect coastlines. In this review, we present an overview of current ecoengineered shoreline design options, the drivers and constraints that influence implementation and factors to consider when evaluating the success of such ecologically engineered shorelines.

Urban shorelines undergo substantial hydrodynamic changes as a result of coastal engineering and shoreline armouring that can alter sedimentation, turbidity, and other factors. These changes often coincide with major shifts in the composition and distribution of marine biota, however, rarely are hydrodynamic-mediated factors confirmed experimentally as the mechanism underpinning these shifts. This study first characterized hydrodynamic-related distribution patterns among epilithic and epiphytic microinvertebrates on urban seawalls in Singapore. We found reduced microinvertebrate abundances and distinct microinvertebrate community structure within benthic turf algae in areas where coastal defences had reduced wave energy and increased sediment deposition, among other hydrodynamic-related abiotic changes. Low-exposure areas also had reduced densities of macroinvertebrate grazers and less dense turf algae (lower mass per cm2) than adjacent high-exposure areas. Using harpacticoid copepods as a model taxon, we performed a reciprocal transplant experiment to discern between the effects of exposure-related conditions and grazing. Results from the experiment indicate that conditions associated with restricted wave energy from shoreline engineering limit harpacticoid population densities, as transplantation to low-exposure areas led to rapid reductions in abundance. At the same time, we found no effect from grazer exclusion cages, suggesting harpacticoids are minimally impacted by exposure-related gradients in gastropod macrograzer densities over short time scales. Given the key role of intertidal microinvertebrates, particularly harpacticoids, in nearshore food webs, we postulate that human-engineered hydrodynamic regimes are an important factor shaping marine ecosystem functioning in urban areas.

Green spaces and agronomy have long been used in terrestrial urban environments to help mitigate the negative effects of urbanization on social-ecological systems. However, they represent an unexplored frontier in marine urban environments, which are also central to human–environment interactions in coastal cities. We evaluated the feasibility and potential environmental impacts of integrating small-scale seaweed farming into urban seawalls. We developed and tested the efficacy of a prototype “planter” unit for cultivating the red, agar-producing seaweed, Hydropuntia edulis, above its typical tidal range on urban seawalls in Singapore. Field trial results suggest that H. edulis can be successfully grown in the mid- and upper-intertidal zones on seawalls by using planters with water-retaining features. However, based on results from life cycle assessment (LCA) and integrated biological models of seaweed production, we found that the choice of materials for constructing planters and their positioning on the seawall were critical in determining net environmental impacts. Farmed seaweeds had an impressive capacity for carbon, nutrient, and metal uptake according to model estimates, but these benefits were outweighed by emissions from energy- and contaminant-intensive materials that are commonly used in seawall “eco-engineering.” At low tidal heights, farmed seaweeds were also more readily dislodged, potentially leading to greater flux of detrital biomass to adjacent systems. This work highlights both the potential of seaweed farming for enhancing the multifunctionality of urban waterfronts, and the importance of objectively weighing overall environmental consequences of such approaches before advancing them as eco-engineering solutions.

Populations of sea cucumbers in Thailand have been declining because of overfishing in recent years; however, little is known about the possible long-term effects of this decline on the sea cucumber population and reef communities. The purpose of this study was to examine the distribution patterns and habitat compositions of Holothuria atra in the upper Gulf of Thailand. In addition, field and laboratory experiments were conducted to investigate the impact of sea cucumber density and feeding activity on the sedimentary microalgal community. The results showed that there was a correlation between the density of H. atra and substrate composition. The density of H. atra increased as the percentage of sand cover in the habitats increased. High concentrations of chlorophyll–a were detected in gut contents. In addition, results from field and laboratory experiments showed that when H. atra was absent, a high concentration of chlorophyll-a in the reef sediment was recorded. The higher the number of H. atra, the greater the capability to reduce the microalgal biomass in the sediment. Thus, H. atra plays an important role in recycling nutrient in reefs in the Gulf of Thailand, and consequently, a decline in the sea cucumber population may alter the reef community.

Given predicted increases in urbanization in tropical and subtropical regions, understanding the processes shaping urban coral reefs may be essential for anticipating future conservation challenges. We used a case study approach to identify unifying patterns of urban coral reefs and clarify the effects of urbanization on hard coral assemblages. Data were compiled from 11 cities throughout East and Southeast Asia, with particular focus on Singapore, Jakarta, Hong Kong, and Naha (Okinawa). Our review highlights several key characteristics of urban coral reefs, including “reef compression” (a decline in bathymetric range with increasing turbidity and decreasing water clarity over time and relative to shore), dominance by domed coral growth forms and low reef complexity, variable city-specific inshore-offshore gradients, early declines in coral cover with recent fluctuating periods of acute impacts and rapid recovery, and colonization of urban infrastructure by hard corals. We present hypotheses for urban reef community dynamics and discuss potential of ecological engineering for corals in urban areas.

Chordomas are rare, malignant bone tumors of the skull-base and axial skeleton. Until recently, there was no consensus among experts regarding appropriate clinical management of chordoma, resulting in inconsistent care and suboptimal outcomes for many patients. To address this shortcoming, the European Society of Medical Oncology (ESMO) and the Chordoma Foundation, the global chordoma patient advocacy group, convened a multi-disciplinary group of chordoma specialists to define by consensus evidence-based best practices for the optimal approach to chordoma. In January 2015, the first recommendations of this group were published, covering the management of primary and metastatic chordomas. Additional evidence and further discussion were needed to develop recommendations about the management of local-regional failures. Thus, ESMO and CF convened a second consensus group meeting in November 2015 to address the treatment of locally relapsed chordoma. This meeting involved over 60 specialists from Europe, the United States and Japan with expertise in treatment of patients with chordoma. The consensus achieved during that meeting is the subject of the present publication and complements the recommendations of the first position paper.

Bycatch and resultant discard mortality are issues of global concern. The groundfish demersal trawl fishery on the west coast of the United States is a multispecies fishery with significant catch of target and nontarget species. These catches are of particular concern in regard to species that have previously been declared overfished and are currently rebuilding biomass back to target levels. To understand these interactions better, we used data from the West Coast Groundfish Observer Program in a series of cluster analyses to evaluate 3 questions: 1) Are there identifiable associations between species caught in the bottom trawl fishery; 2) Do species that are undergoing population rebuilding toward target biomass levels (“rebuilding species”) cluster with targeted species in a consistent way; 3) Are the relationships between rebuilding bycatch species and target species more resolved at particular spatial scales or are relationships spatially consistent across the whole data set? Two strong species clusters emerged—a deepwater slope cluster and a shelf cluster—neither of which included rebuilding species. The likelihood of encountering rebuilding rockfish species is relatively low. To evaluate whether weak clustering of rebuilding rockfish was attributable to their low rate of occurrence, we specified null models of species occurrence. Results indicated that the ability to predict occurrence of rebuilding rockfish when target species were caught was low. Cluster analyses performed at a variety of spatial scales indicated that the most reliable clustering of rebuilding species was at the spatial scale of individual fishing ports. This finding underscores the value of spatially resolved data for fishery management.

Quantifying discarded catch is needed to guide effective fishery management and recognize the unintended impacts of fishing; ultimately to promote a more sustainable fishery. To understand fishing mortality prior to the establishment of an IFQ management system, we provide estimates of discarded and total catch (sum of discard and landings) in the U.S. west coast groundfish demersal trawl fishery from 2002 to 2009. West Coast Groundfish Observer Program (WCGOP) data were expanded to fleet-level discard estimates using a ratio estimator. Total estimated discard in the fishery declined by 52% across the study period. On average, 29% of the annual groundfish catch was discarded at-sea. A high proportion of catch was discarded during 2002, but subsequently overall discard decreased even though fishing effort (landings and trawl tow hours) increased in the fishery from 2004 to 2009. The largest components of discard (by weight) were Pacific hake (Merluccius productus), arrowtooth flounder (Atheresthes stomias), skates (Rajidae sp.) and spiny dogfish (Squalus acanthias). In 2009 relative to 2002, the discarded fraction of catch for rebuilding species, which constrain the fishery, had increased by 39%. In contrast, the discarded fraction of catch for target species had decreased by 24%. In addition, much of the fishing effort shifted to deeper waters. Our results represent a baseline for future comparisons as the fishery shifted from trip limit management to an Individual Fishing Quota (IFQ) program in 2011.

Length frequency data are a central component of many statistical age-structured models, which are used widely to conduct fisheries stock assessments and produce estimates of stock status for management. However, these data can be biased due to systematic errors during the sampling process. This study examined how bias in length frequency data affected stock status estimates from an age-structured assessment model and subsequent prescribed management actions. A simulation approach was used to test the effect of two different scenarios of bias on assessment results. Populations were simulated based on life history parameters for three different serranid species in the southeastern United States and followed a trajectory that increased and then decreased over time. From these simulated populations, fishery-dependent length frequency data were generated and then altered to represent different types of systematic sampling error. Data that were biased towards larger fish had a considerable effect on t...

Background Tumor EGFR and KRas mutations are both predictive and prognostic biomarkers in patients with advanced NSCLC. We analyzed the correlation between these biomarkers and treatment outcomes in a phase III trial of 3rd/4th line sorafenib in patients with NSCLC. Methods The global, randomized, placebo-controlled MISSION trial enrolled 703 patients with advanced relapsed/refractory NSCLC of predominantly non-squamous histology. The primary study endpoint was overall survival (OS). EGFR and KRas mutations were analyzed in archival tumor samples and in circulating tumor DNA isolated from plasma. Results Tumor and/or plasma mutation data were available from 347 patients (49%). EGFR and KRas mutations were detected in 89 (26%) and 68 (20%) patients, respectively, and were well balanced between treatment arms. Analysis of the interaction between EGFR mutation status and treatment effect on survival suggested that patients with EGFR mutations (mEGFR) benefitted from sorafenib, while those with wild-type EGFR (wtEGFR) did not (p = 0.023). Median OS was two-fold longer in mEGFR patients receiving sorafenib versus placebo (423 vs 197 days, HR 0.48, p = 0.002). There was no significant difference in OS between patients with wtEGFR receiving sorafenib or placebo (253 vs 256 days, HR 0.92, p = 0.559). An interaction was also seen between EGFR mutation status and the sorafenib effect on PFS (p = 0.015). Patients with mEGFR treated with sorafenib had better outcomes compared to placebo based on Cox regression analysis (HR 0.27, p Conclusion Post-hoc analyses of efficacy outcomes in MISSION suggest that advanced NSCLC patients with EGFR mutations may derive a survival benefit from receiving 3rd/4th line sorafenib. These results must be interpreted with caution due to the small, non-representative nature of the genetic biomarker subpopulation analyzed in this trial. Further prospective investigation may be warranted. Disclosure T.S.K. Mok: Honoraria: AstraZeneca, Roche, Eli Lilly, Merck Serono, Eisai, BMS, BeiGene, AVEO, Pfizer, Taiho, Boehringer Ingelheim, and GSK Biologicals Speaker: Astrazeneca, Roche, Eli Lilly, Boehringer Ingelheim, and Merck Serono Research funding: Astrazeneca. L. Paz-Ares: Dr. Paz-Ares has received honoraria from Bayer HealthCare Pharmaceuticals, Lilly, Roche and Pfizer. Y. Wu: Dr. Wu has received lecture fees from Roche, AstraZeneca, Eli Lilly, and Pfizer. V. Hirsh: Member of the steering committee for the MISSION trial. C. Lathia: Dr. Lathia is an employee of Bayer HealthCare. T.J. Ong: Dr. Ong is an employee of, and owns shares in, Bayer HealthCare. C. Pena: Dr. Pena is an employee of Bayer HealthCare. All other authors have declared no conflicts of interest.