Adaptive spatiotemporal management to reduce shark bycatch in tuna fisheries.

Purse-seine tropical tuna fishing in the eastern tropical Pacific Ocean (EPO) results in the bycatch of several sensitive species groups, including elasmobranchs. Effective ecosystem management balances conservation and resource use and requires considering trade-offs and synergies. Seasonal and adaptive spatial measures can reduce fisheries impacts on nontarget species while maintaining or increasing target catches. Identifying persistently high-risk areas in the open ocean, where dynamic environmental conditions drive changes in species' distributions, is essential for exploring the impact of fisheries closures. We used fisheries observer data collected from 1995 to 2021 to explore the spatiotemporal persistence of areas of high bycatch risk for 2 species of oceanic sharks, silky shark (Carcharhinus falciformis) and oceanic whitetip shark (Carcharhinus longimanus), and of low tuna catch rates. We analyzed data collected by fisheries scientific observers onboard approximately 200 large purse-seine vessels operating in the EPO under 10 different flags. Fishing effort, catch, and bycatch data were aggregated spatially and temporally at 1° × 1° cells and monthly, respectively. When areas of high fishing inefficiency were closed the entire study period and effort was reallocated proportionally to reflect historical effort patterns, yearly tuna catch appeared to increase by 1-11%, whereas bycatch of silky and oceanic whitetip sharks decreased by 10-19% and 9%, respectively. Prior to fishing effort redistribution, bycatch reductions accrued to 21-41% and 14% for silky and oceanic whitetip sharks, respectively. Our results are consistent with previous findings and demonstrate the high potential for reducing elasmobranch bycatch in the EPO without compromising catch rates of target tuna species. They also highlight the need to consider new dynamic and adaptive management measures to more efficiently fulfill conservation and sustainability objectives for exploited resources in the EPO.

Gestión espaciotemporal adaptativa para reducir la captura incidental de tiburones en la pesca del atún Resumen La pesca con cerco del atún tropical en el Pacífico Tropical Oriental (PTO) resulta en la captura incidental de varios grupos de especies sensibles, incluidos los elasmobranquios. La gestión eficiente del ecosistema equilibra la conservación y el uso de recursos y requiere que se consideren las compensaciones y las sinergias. Las medidas espaciales adaptativas y estacionales pueden reducir el impacto de las pesquerías sobre las especies accesorias mientras mantienen o incrementan la captura intencional. La identificación de las áreas con alto riesgo persistente en mar abierto, en donde las condiciones ambientales dinámicas causan cambios en la distribución de las especies, es esencial para explorar el impacto del cierre de las pesquerías. Usamos datos de observadores de las pesquerías recolectados entre 1995 y 2021 para explorar la persistencia espaciotemporal de las áreas con alto riesgo de captura incidental para dos especies de tiburón (Carcharhinus falciformi y C. longimanus) y con tasas bajas de captura de atún. Analizamos los datos recolectados por los observadores científicos de las pesquerías a bordo de aproximadamente 200 embarcaciones grandes de pesca con cerco que operaban en el PTO bajo diez banderas diferentes. Agregamos los datos sobre el esfuerzo de pesca, captura y la captura incidental de forma espacial y temporal en celdas de 1° x 1° y mensual, respectivamente. Cuando las áreas con gran ineficiencia pesquera se encontraban cerradas durante toda la investigación y el esfuerzo se reasignaba proporcionalmente para reflejar los patrones históricos de esfuerzo, el esfuerzo anual de captura de atún parecía incrementar en un 1­11%, mientras que la captura incidental de las dos especies de tiburones disminuía en un 10­19% (C. falciformi) y 9% (C. longimanus). Antes de que de redistribuyera el esfuerzo de pesca, la reducción de la captura incidental se acumuló hasta el 21­41% (C. falciformi) y 14% (C. longimanus). Nuestros resultados son congruentes con resultados previos y demuestran el gran potencial de reducción de la captura incidental de elasmobranquios en el PTO sin poner en peligro las tasas de captura de las especies de atún. Los resultados también enfatizan la necesidad de considerar medidas adaptativas nuevas y dinámicas para cumplir de forma más eficiente los objetivos de conservación y sustentabilidad para la explotación de recursos en el PTO.

Tracking elusive and shifting identities of the global fishing fleet.

Illegal, unreported, and unregulated (IUU) fishing costs billions of dollars per year and is enabled by vessels obfuscating their identity. Here, we combine identities of ~35,000 vessels with a decade of GPS data to provide a global assessment of fishing compliance, reflagging patterns, and fishing by foreign-owned vessels. About 17% of high seas fishing is by potentially unauthorized or internationally unregulated vessels, with hot spots of this activity in the west Indian and the southwest Atlantic Oceans. In addition, reflagging, a tactic often used to obscure oversight, occurs in just a few ports primarily by fleets with high foreign ownership. Fishing by foreign-owned vessels is concentrated in parts of high seas and certain national waters, often flying flags of convenience. These findings can address the global scope of potential IUU fishing and enable authorities to improve oversight.

SARS-CoV-2 infection in patients with melanoma: results of the Spanish Melanoma Group registry.

BACKGROUND: The Spanish Melanoma Group (GEM) developed a national registry of patients with melanoma infected by SARS-CoV-2 ("GRAVID"). METHODS: The main objective was to describe the COVID-19 fatality rate in patients with melanoma throughout the pandemic, as well as to explore the effect of melanoma treatment and tumor stage on the risk of COVID-19 complications. These are the final data of the register, including cases from February 2020 to September 2021. RESULTS: One hundred-fifty cases were registered. Median age was 68 years (range 6-95), 61 (40%) patients were females, and 63 (42%) patients had stage IV. Thirty-nine (26%) were on treatment with immunotherapy, and 17 (11%) with BRAF-MEK inhibitors. COVID-19 was resolved in 119 cases, including 85 (57%) patients cured, 15 (10%) that died due to melanoma, and 20 (13%) that died due to COVID-19. Only age over 60 years, cardiovascular disorders, and diabetes mellitus increased the risk of death due to COVID-19, but not advanced melanoma stage nor melanoma systemic therapies. Three waves have been covered by the register: February-May 2020, August-November 2020, and December 2020-April 2021. The first wave had the highest number of registered cases and COVID-19 mortality. CONCLUSION: Tumor stage or melanoma treatments are non-significant prognostic factors for COVID-19 mortality. During the pandemic in Spain there was a downward trend in the number of patients registered across the waves, as well as in the severity of the infection. GOV IDENTIFIER: NCT04344002.

Initial clinical and treatment patterns of advanced differentiated thyroid cancer: ERUDIT study.

Background: Up to 30% of differentiated thyroid cancer (DTC) will develop advanced-stage disease (aDTC) with reduced overall survival (OS). Objective: The aim of this study is to characterize initial diagnosis of aDTC, its therapeutic management, and prognosis in Spain and Portugal. Methods: A multicentre, longitudinal, retrospective study of adult patients diagnosed with aDTC in the Iberian Peninsula was conducted between January 2007 and December 2012. Analyses of baseline characteristics and results of initial treatments, relapse- or progression-free survival ((RP)FS) from first DTC diagnosis, OS, and prognostic factors impacting the evolution of advanced disease were evaluated. Results: Two hundred and thirteen patients (median age: 63 years; 57% female) were eligible from 23 hospitals. Advanced disease presented at first diagnosis (de novo aDTC) included 54% of patients, while 46% had relapsed from early disease (recurrent/progressive eDTC). At initial stage, most patients received surgery (98%) and/or radioiodine (RAI) (89%), with no differences seen between median OS (95% CI) (10.4 (7.3-15.3) years) and median disease-specific-survival (95% CI) (11.1 (8.7-16.2) years; log-rank test P = 0.4737). Age at diagnosis being <55 years was associated with a lower risk of death (Wald chi-square (Wc-s) P < 0.0001), while a poor response to RAI to a higher risk of death ((Wc-s) P < 0.05). In the eDTC cohort, median (RP)FS (95% CI) was of 1.7 (1.0-2.0) years after RAI, with R0/R1 surgeries being the only common significant favourable factor for longer (RP)FS and time to aDTC ((Wc-s) P < 0.05). Conclusion: Identification of early treatment-dependent prognostic factors for an unfavourable course of advanced disease is possible. An intensified therapeutic attitude may reverse this trend and should be considered in poor-performing patients. Prospective studies are required to confirm these findings.

Scientific mobilization of keystone actors for biosphere stewardship.

The biosphere crisis requires changes to existing business practices. We ask how corporations can become sustainability leaders, when constrained by multiple barriers to collaboration for biosphere stewardship. We describe how scientists motivated, inspired and engaged with ten of the world's largest seafood companies, in a collaborative process aimed to enable science-based and systemic transformations (2015-2021). CEOs faced multiple industry crises in 2015 that incentivized novel approaches. New scientific insights, an invitation to collaborate, and a bold vision of transformative change towards ocean stewardship, created new opportunities and direction. Co-creation of solutions resulted in new knowledge and trust, a joint agenda for action, new capacities, international recognition, formalization of an organization, increased policy influence, time-bound goals, and convergence of corporate change. Independently funded scientists helped remove barriers to cooperation, provided means for reflection, and guided corporate strategies and actions toward ocean stewardship. By 2021, multiple individuals exercised leadership and the initiative had transitioned from preliminary and uncomfortable conversations, to a dynamic, operational organization, with capacity to perform global leadership in the seafood industry. Mobilizing transformational agency through learning, collaboration, and innovation represents a cultural evolution with potential to redirect and accelerate corporate action, to the benefit of business, people and the planet.

External Validity of Somatostatin Analogs Trials in Advanced Neuroendocrine Neoplasms: The GETNE-TRASGU Study.

INTRODUCTION: Somatostatin analogs (SSA) prolong progression-free survival (PFS) in patients with well-differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, the eligibility criteria in randomized clinical trials (RCTs) have been restricted, which contrasts with the vast heterogeneity found in NENs. METHODS: We identified patients with well-differentiated (Ki-67% ≤20%), metastatic GEP-NENs treated in first line with SSA monotherapy from the Spanish R-GETNE registry. The therapeutic effect was evaluated using a Bayesian Cox model. The objective was to compare survival-based outcomes from real-world clinical practice versus RCTs. RESULTS: The dataset contained 535 patients with a median age of 62 years (range: 26-89). The median Ki-67% was 4 (range: 0-20). The most common primary tumor sites were as follows: midgut, 46%; pancreas, 34%; unknown primary, 10%; and colorectal, 10%. Half of the patients received octreotide LAR (n = 266) and half, lanreotide autogel (n = 269). The median PFS was 28.0 months (95% CI: 22.1-32.0) for octreotide versus 30.1 months (95% CI: 23.1-38.0) for lanreotide. The overall hazard ratio for lanreotide versus octreotide was 0.90 (95% credible interval: 0.71-1.12). The probability of effect sizes >30% with lanreotide versus octreotide was 2 and 6% for midgut and foregut NENs, respectively. CONCLUSION: Our study evaluated the external validity of RCTs examining SSAs in the real world, as well as the main effect-modifying factors (progression status, symptoms, tumor site, specific metastases, and analytical data). Our results indicate that both octreotide LAR and lanreotide autogel had a similar effect on PFS. Consequently, both represent valid alternatives in patients with well-differentiated, metastatic GEP-NENs.

Durable Response to Vemurafenib and Cobimetinib for the Treatment of BRAF-Mutated Metastatic Melanoma in Routine Clinical Practice.

BACKGROUND: The combination of BRAF and MEK inhibitors delays the onset of resistance and provides more sustained and dramatic responses in comparison with a BRAF inhibitor in monotherapy. The objective of the study was to evaluate the effectiveness of the combination therapy with vemurafenib/cobimetinib in terms of durability, and to describe differential characteristics in patients associated to durable responses in real-world settings. PATIENTS AND METHODS: Retrospective, observational, cross-sectional, multicenter study involving 41 patients with advanced melanoma harboring a BRAF V600 mutation who initiated a combination therapy with vemurafenib/cobimetinib between May 2018 and March 2019. Participants were differentiated regarding the durability of the response: durable (complete response, CR, or a partial response, PR, for at least 12 months) and non-durable (stable disease, SD, progressive disease, PD, or CR/PR <12 months). Secondary endpoints included treatment adherence, labor productivity, anxiety/depression, and safety profile. RESULTS: During the combination therapy, 12 patients (29.3%) had a CR, 19 a PR (46.3%), 5 showed SD (12.2%), and 5 had PD. A total of 12 patients (29.3%) were considered as achieving a durable response and 29 (70.7%) as a non-durable one. Practically all sociodemographic and clinical characteristics were similar between patients. Body mass index was the only differential factor (with higher body mass index achieving a non-durable response). The treatment adherence was 100% in patients with durable response and 66.7% in those with non-durable. CONCLUSION: The combination treatment with vemurafenib/cobimetinib results in an important impact on long-term survival, leading to a steady CR in one-third of the patients.

Circulating Levels of the Interferon-γ-Regulated Chemokines CXCL10/CXCL11, IL-6 and HGF Predict Outcome in Metastatic Renal Cell Carcinoma Patients Treated with Antiangiogenic Therapy.

Sunitinib and pazopanib are standard first-line treatments for patients with metastatic renal cell carcinoma (mRCC). Nonetheless, as the number of treatment options increases, there is a need to identify biomarkers that can predict drug efficacy and toxicity. In this prospective study we evaluated a set of biomarkers that had been previously identified within a secretory signature in mRCC patients. This set includes tumor expression of c-Met and serum levels of HGF, IL-6, IL-8, CXCL9, CXCL10 and CXCL11. Our cohort included 60 patients with mRCC from 10 different Spanish hospitals who received sunitinib (n = 51), pazopanib (n = 4) or both (n = 5). Levels of biomarkers were studied in relation to response rate, progression-free survival (PFS) and overall survival (OS). High tumor expression of c-Met and high basal serum levels of HGF, IL-6, CXCL11 and CXCL10 were significantly associated with reduced PFS and/or OS. In multivariable Cox regression analysis, CXCL11 was identified as an independent biomarker predictive of shorter PFS and OS, and HGF was an independent predictor of reduced PFS. Correlation analyses using our cohort of patients and patients from TCGA showed that HGF levels were significantly correlated with those of IL-6, CXCL11 and CXCL10. Bioinformatic protein-protein network analysis revealed a significant interaction between these proteins, all this suggesting a coordinated expression and secretion. We also developed a prognostic index that considers this group of biomarkers, where high values in mRCC patients can predict higher risk of relapse (HR 5.28 [2.32-12.0], p < 0.0001). In conclusion, high plasma HGF, CXCL11, CXCL10 and IL-6 levels are associated with worse outcome in mRCC patients treated with sunitinib or pazopanib. Our findings also suggest that these factors may constitute a secretory cluster that acts coordinately to promote tumor growth and resistance to antiangiogenic therapy.

Physician-perceived utility of the EORTC QLQ-GINET21 questionnaire in the treatment of patients with gastrointestinal neuroendocrine tumours: a multicentre, cross-sectional survey (QUALINETS).

BACKGROUND AND OBJECTIVE: Patient-reported outcome measures can provide clinicians with valuable information to improve doctor-patient communication and inform clinical decision-making. The aim of this study was to evaluate the physician-perceived utility of the QLQ-GINET21 in routine clinical practice in patients with gastrointestinal neuroendocrine tumours (GI-NETs). Secondary aims were to explore the patient, clinician, and/or centre-related variables potentially associated with perceived clinical utility. METHODS: Non-interventional, cross-sectional, multicentre study conducted at 34 hospitals in Spain and Portugal (NCT02853422). Patients diagnosed with GI-NETs completed two health-related quality of life (HRQoL) questionnaires (QLQ-C30, QLQ-GINET21) during a single routine visit. Physicians completed a 14-item ad hoc survey to rate the clinical utility of QLQ-GINET21 on three dimensions: 1)therapeutic and clinical decision-making, 2)doctor-patient communication, 3)questionnaire characteristics. RESULTS: A total of 199 patients at 34 centres were enrolled by 36 participating clinicians. The highest rated dimension on the QLQ-GINET21 was questionnaire characteristics (86.9% of responses indicating "high utility"), followed by doctor-patient communication (74.4%), and therapeutic and clinical decision-making (65.8%). One physician-related variable (GI-NET patient volume > 30 patients/year) was associated with high clinical utility and two variables (older age/less experience treating GI-NETs) with low clinical utility. CONCLUSIONS: Clinician-perceived clinical utility of QLQ-GINET21 is high. Clinicians valued the instruments' capacity to provide a better understanding of patient perspectives and to identify the factors that had the largest influence on patient HRQoL.

Preferences for Renal Cell Carcinoma Pharmacological Treatment: A Discrete Choice Experiment in Patients and Oncologists.

INTRODUCTION: The purpose of this investigation was to explore patients' and oncologists' preferences for the characteristics of a pharmacological regimen for patients with advanced renal cell carcinoma (aRCC). MATERIAL AND METHODS: Cross-sectional observational study based on a discrete choice experiment (DCE) conducted in Spain. A literature review, a focus group with oncologists and interviews with patients informed the DCE design. Five attributes were included: progression survival gain, risk of serious adverse events (SAEs), health-related quality of life (HRQoL), administration mode, and treatment cost. Preferences were analyzed using a mixed-logit model to estimate relative importance (RI) of attributes (importance of an attribute in relation to all others), which was compared between aRCC patients and oncologists treating aRCC. Willingness to pay (WTP, payer: health system) for a benefit in survival or in risk reduction and maximum acceptable risk (MAR) in SAEs for improving survival were estimated from the DCE. Subgroup analyses were performed to identify factors that influence preference. RESULTS: A total of 105 patients with aRCC (77.1% male, mean age 65.9 years [SD: 10.4], mean time since RCC diagnosis 6.3 years [SD: 6.1]) and 67 oncologists (52.2% male, mean age 41.9 years [SD: 8.4], mean duration of experience in RCC 10.2 years [SD: 7.5]) participated in the study. The most important attribute for patients and oncologists was survival gain (RI: 43.6% vs. 54.7% respectively, p<0.05), followed by HRQoL (RI: 35.5% vs. 18.0%, respectively, p<0.05). MAR for SAEs was higher among oncologists than patients, while WTP (for the health system) was higher for patients. Differences in preferences were found according to time since diagnosis and education level (patients) or length of professional experience (oncologists). CONCLUSION: Patients' and oncologists' preferences for aRCC treatment are determined mainly by the efficacy (survival gain) but also by the HRQoL provided. The results of the study can help to inform decision-making in the selection of appropriate aRCC treatment.

Usefulness of an immunohistochemical score in advanced pancreatic neuroendocrine tumors treated with CAPTEM or everolimus.

BACKGROUND: Pancreatic neuroendocrine tumors are rare neoplasms for which few predictive and/or prognostic biomarkers have been validated. Our previous work suggested the potential of the combined expression of N-myc downstream-regulated gen-1 (NDRG-1), O6-methylguanine DNA methyltransferase (MGMT) and Pleckstrin homology-like domain family A member 3 (PHLDA-3) as prognostic factors for relapse and survival. METHODS: In this new multicenter study we evaluated immunohistochemistry expression in 76 patients with advanced PanNET who were treated with capecitabine-temozolomide or everolimus. Based on the immunohistochemistry panel, an immunohistochemistry prognostic score (IPS) was developed. RESULTS: In patients treated with capecitabine and temozolomide, low IPS was an independent prognostic factor for progression-free-survival and overall-survival. Similar findings were observed with highest IPS for overall-survival in patients treated with everolimus. CONCLUSION: From our knowledge, it is the first time that a simple IPS could be useful to predict outcome for patients with metastatic pancreatic neuroendocrine tumors treated with everolimus or capecitabine and temozolomide.

Integrating climate adaptation and biodiversity conservation in the global ocean.

The impacts of climate change and the socioecological challenges they present are ubiquitous and increasingly severe. Practical efforts to operationalize climate-responsive design and management in the global network of marine protected areas (MPAs) are required to ensure long-term effectiveness for safeguarding marine biodiversity and ecosystem services. Here, we review progress in integrating climate change adaptation into MPA design and management and provide eight recommendations to expedite this process. Climate-smart management objectives should become the default for all protected areas, and made into an explicit international policy target. Furthermore, incentives to use more dynamic management tools would increase the climate change responsiveness of the MPA network as a whole. Given ongoing negotiations on international conservation targets, now is the ideal time to proactively reform management of the global seascape for the dynamic climate-biodiversity reality.

The importance of migratory connectivity for global ocean policy.

The distributions of migratory species in the ocean span local, national and international jurisdictions. Across these ecologically interconnected regions, migratory marine species interact with anthropogenic stressors throughout their lives. Migratory connectivity, the geographical linking of individuals and populations throughout their migratory cycles, influences how spatial and temporal dynamics of stressors affect migratory animals and scale up to influence population abundance, distribution and species persistence. Population declines of many migratory marine species have led to calls for connectivity knowledge, especially insights from animal tracking studies, to be more systematically and synthetically incorporated into decision-making. Inclusion of migratory connectivity in the design of conservation and management measures is critical to ensure they are appropriate for the level of risk associated with various degrees of connectivity. Three mechanisms exist to incorporate migratory connectivity into international marine policy which guides conservation implementation: site-selection criteria, network design criteria and policy recommendations. Here, we review the concept of migratory connectivity and its use in international policy, and describe the Migratory Connectivity in the Ocean system, a migratory connectivity evidence-base for the ocean. We propose that without such collaboration focused on migratory connectivity, efforts to effectively conserve these critical species across jurisdictions will have limited effect.

Prediction of Progression-Free Survival in Patients With Advanced, Well-Differentiated, Neuroendocrine Tumors Being Treated With a Somatostatin Analog: The GETNE-TRASGU Study.

PURPOSE: Somatostatin analogs (SSAs) are recommended for the first-line treatment of most patients with well-differentiated, gastroenteropancreatic (GEP) neuroendocrine tumors; however, benefit from treatment is heterogeneous. The aim of the current study was to develop and validate a progression-free survival (PFS) prediction model in SSA-treated patients. PATIENTS AND METHODS: We extracted data from the Spanish Group of Neuroendocrine and Endocrine Tumors Registry (R-GETNE). Patient eligibility criteria included GEP primary, Ki-67 of 20% or less, and first-line SSA monotherapy for advanced disease. An accelerated failure time model was developed to predict PFS, which was represented as a nomogram and an online calculator. The nomogram was externally validated in an independent series of consecutive eligible patients (The Christie NHS Foundation Trust, Manchester, United Kingdom). RESULTS: We recruited 535 patients (R-GETNE, n = 438; Manchester, n = 97). Median PFS and overall survival in the derivation cohort were 28.7 (95% CI, 23.8 to 31.1) and 85.9 months (95% CI, 71.5 to 96.7 months), respectively. Nine covariates significantly associated with PFS were primary tumor location, Ki-67 percentage, neutrophil-to-lymphocyte ratio, alkaline phosphatase, extent of liver involvement, presence of bone and peritoneal metastases, documented progression status, and the presence of symptoms when initiating SSA. The GETNE-TRASGU (Treated With Analog of Somatostatin in Gastroenteropancreatic and Unknown Primary NETs) model demonstrated suitable calibration, as well as fair discrimination ability with a C-index value of 0.714 (95% CI, 0.680 to 0.747) and 0.732 (95% CI, 0.658 to 0.806) in the derivation and validation series, respectively. CONCLUSION: The GETNE-TRASGU evidence-based prognostic tool stratifies patients with GEP neuroendocrine tumors receiving SSA treatment according to their estimated PFS. This nomogram may be useful when stratifying patients with neuroendocrine tumors in future trials. Furthermore, it could be a valuable tool for making treatment decisions in daily clinical practice.

Outstanding Challenges in the Transferability of Ecological Models.

Predictive models are central to many scientific disciplines and vital for informing management in a rapidly changing world. However, limited understanding of the accuracy and precision of models transferred to novel conditions (their 'transferability') undermines confidence in their predictions. Here, 50 experts identified priority knowledge gaps which, if filled, will most improve model transfers. These are summarized into six technical and six fundamental challenges, which underlie the combined need to intensify research on the determinants of ecological predictability, including species traits and data quality, and develop best practices for transferring models. Of high importance is the identification of a widely applicable set of transferability metrics, with appropriate tools to quantify the sources and impacts of prediction uncertainty under novel conditions.

The environmental niche of the global high seas pelagic longline fleet.

International interest in the protection and sustainable use of high seas biodiversity has grown in recent years. There is an opportunity for new technologies to enable improvements in management of these areas beyond national jurisdiction. We explore the spatial ecology and drivers of the global distribution of the high seas longline fishing fleet by creating predictive models of the distribution of fishing effort from newly available automatic identification system (AIS) data. Our results show how longline fishing effort can be predicted using environmental variables, many related to the expected distribution of the species targeted by longliners. We also find that the longline fleet has seasonal environmental preferences (for example, increased importance of cooler surface waters during boreal summer) and may only be using 38 to 64% of the available environmentally suitable fishing habitat. Possible explanations include misclassification of fishing effort, incomplete AIS coverage, or how potential range contractions of pelagic species may have reduced the abundance of fishing habitats in the open ocean.

Interferon gamma, an important marker of response to immune checkpoint blockade in non-small cell lung cancer and melanoma patients.

BACKGROUND: Programmed death-ligand 1 (PD-L1) may be induced by oncogenic signals or can be upregulated via interferon gamma (IFN-γ). We have explored whether the expression of IFNG, the gene encoding IFN-γ, is associated with clinical response to the immune checkpoint blockade in non-small cell lung cancer (NSCLC) and melanoma patients. The role of inflammation-associated transcription factors STAT3, IKBKE, STAT1 and other associated genes has also been examined. METHODS: Total RNA from 17 NSCLC and 21 melanoma patients was analyzed by quantitative reverse transcription PCR. STAT3 and Rantes, YAP1 and CXCL5, DNMT1, RIG1 and TET1, EOMES, IFNG, PD-L1 and CTLA4, IKBKE and NFATC1 mRNA were examined. PD-L1 protein expression in tumor and immune cells and stromal infiltration of CD8+ T-cells were also evaluated. Progression-free survival and overall survival were estimated. RESULTS: A total of 17 NSCLC patients received nivolumab and 21 melanoma patients received pembrolizumab. Progression-free survival with nivolumab was significantly longer in NSCLC patients with high versus low IFNG expression (5.1 months versus 2 months, p = 0.0124). Progression-free survival with pembrolizumab was significantly longer in melanoma patients with high versus low IFNG expression (5.0 months versus 1.9 months, p = 0.0099). Significantly longer overall survival was observed for melanoma patients with high versus low IFNG expression (not reached versus 10.2 months p = 0.0183). There was a trend for longer overall survival for NSCLC patients with high versus low IFNG expression. CONCLUSIONS: IFN-γ is an important marker for prediction of response to immune checkpoint blockade. Further research is warranted in order to validate whether IFNG is more accurate than PD-L1.

Capecitabine and temozolomide in grade 1/2 neuroendocrine tumors: a Spanish multicenter experience.

BACKGROUND & METHODS: Capecitabine and temozolomide chemotherapy was used in 65 patients with grade 1/2 neuroendocrine tumors (NETs). 46 patients (70.8%) had pancreatic NETs (pNETs). RESULTS: Response rate was 47.7%, with two complete responses (3.1%), 29 partial responses (44.6%) and 27 patients (41.5%) achieved stable disease. Median progression-free survival was 16.1 months (95% CI: 10.7-21.6) and overall survival was 38.3 months (95% CI: 24.6-51.9). Differences in progression-free survival and overall survival between pNETs and non-pNETs were not found. Nine (13.8%) patients experienced grade 3/4 toxicities, mainly thrombocytopenia (10.8%) and neutropenia (7.7%). CONCLUSION: This is the largest reported series of NETs treated with capecitabine and temozolomide in daily practice and shows that this combination is a promising treatment option for both grade 1/2 pNETs and non-pNETs.