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The European Dendroecological Fieldweek (EDF) is a one-week course that takes place every year at varying locations in Europe according to the principle "Bring tree-ring research to the people”. The EDF welcomes early-career to advanced researchers, but also forest service and other federal agency employees and private people interested in tree-ring sciences from all over the world. It encompasses a large spectrum of dendrochronological field, laboratory and data analysis methods and scientific fields including climatology, ecology, physiology, geomorphology and archaeology. Multiple scales of observations from the individual cell to the ecosystem level and from seasonal to multi-centennial periods are covered. Work on mini research projects in topic groups alternates with keynote lectures and individual participants' presentations. As one of the first in-person tree-ring meetings since the start of the COVID-19 pandemic the 31st EDF was held in summer 2021 in Val Müstair, Switzerland. Topics included i) Tree age and climate sensitivity of a relict, old-growth Scots pine stand, ii) Blue intensity-based climate sensitivity of Norway spruce growth, iii) Tree rings as indicators of grey larch budmoth outbreaks, iv) Growth of larch trees along an abandoned irrigation channel, v) Wood anatomical characteristics of two alpine creeping shrub species, and vi) Historical dating of a stable and a residential house. Alongside with their educational value these projects allowed novel insight into the age structure and growth dynamics of the sub-alpine forests and beyond in the valley and provided valuable outcome to the local stakeholders such as the Nature Park Biosfera Val Müstair, the local forest service and the public of Val Müstair. Under hindered conditions due to the pandemic, the 31st EDF still demonstrated its strength as an international educational and interdisciplinary scientific field and lab course, combining teaching with the application of cutting-edge technologies. © 2023
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Background: High-grade glioma patients and their caregivers often suffer from psychological distress.1 Nevertheless, supportive services are lacking. This study investigates whether a mindfulness-based yoga intervention is feasible and affects anxiety, depression, quality of life, and stress-associated physiological parameters. Method(s): A monocentric on-site pilot study to test feasibility was started in 2020 and then adapted to an online format due to the COVID-19 pandemic. Participants were randomly assigned to immediate intervention and 8-weeks wait-list control groups. At randomization, immediately before and after the end of the 8-week intervention (1 h/week), which was performed by trained yoga teachers in a synchronous format, as well as another 3 months later, validated questionnaires were filled by participants and serum plus saliva samples were taken. In addition, participants were asked to rate their satisfaction with various course features. Result(s): A total of 43 participants with 27 donating biological samples and a drop-out of 14 were included. No significant changes in subjective criteria and physiological stress parameters were detected. Known disadvantages of online interventions were reported, e.g. technical difficulties. Overall course-satisfaction, with teachers guidance most positively rated, was reported. Discussion(s): High-grade glioma patients are very vulnerable due to their rapidly changing health status. Caregivers often have very limited time due to the care they provide. Therefore, recruitment is difficult and leads to dropouts. Validity of the results may be limited due to the small sample size and comparability of stress parameters due to circadian fluctuations in salivary cortisol. Conclusion(s): The online yoga course is feasible. Despite of lacking personal contact, supervision of participants is possible and satisfactory. To measure cortisol, more reliable hair samples will be taken in the upcoming multicenter study, starting in fall 2021.
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Background: Post-COVID syndrome (PCS) is an increasingly recognised complication of acute SARS-CoV- 2 infection, characterised by persistent fatigue, reduced exercise tolerance, chest pain, shortness of breath and cognitive slowing. Acute COVID-19 is strongly linked with increased risk of thrombosis;a prothrombotic state. Elevated Von Willebrand Factor (VWF) Antigen (Ag):ADAMTS13 ratio is associated with severity of acute COVID-19 infection. Aim(s): We hypothesised that the pro-thrombotic state is implicated in the pathogenesis of PCS. We investigated specialist coagulation parameters associated with reduced exercise capacity in patients with PCS to identify the utility of these parameters to determine ongoing disease activity. We also investigated if an association exists between elevated VWF(Ag):ADAMTS13 ratio and impaired exercise capacity in patients with PCS. Method(s): Retrospective analysis of VWF(Ag):ADAMTS13 ratio in patients with PCS at a dedicated post-COVID clinic. VWF(Ag):ADAMTS13 ratio was correlated with symptoms including exercise capacity as assessed by 1 minute sit-to- stand (STS) test and/or 6 minute walk test (6MWT). Peripheral oxygen desaturation >=3% for 6MWT and STS test, and increase in lactate>1 from baseline during 6MWT were taken as markers of impaired exercise capacity. Result(s): Elevated VWF(Ag):ADAMTS13 ratio (>=1.5) was found to be four times (OR 4.3) more likely in patients with impaired exercise capacity. 20% (56/276) had impaired exercise capacity, of which 55% (31/56) had a raised VWF(Ag):ADAMTS13 ratio >=1.5 (p < 0.0001). A higher median VWF(Ag):ADAMTS13 ratio of 1.5 (IQR 1.2-1.7) in patients with abnormal exercise testing compared to 1.1 (IQR 0.9-1.4) in patients with normal exercise testing was found (p < 0.0001). FVIII and VWF(Ag) were elevated in 26% and 18% respectively and support a hypercoagulable state in patients with PCS. Conclusion(s): These findings suggest possible ongoing microvascular/ endothelial dysfunction in the pathogenesis of PCS and highlight the potential role for prophylactic anticoagulation in the management of these patients.
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Background: Patients with cancer have high rates of healthcare utilization due to complications of disease and treatment. Early identification of patient illness may help reduce acute care use and improve quality of care. Remote patient monitoring (RPM), a type of telemedicine involving collection and transmission of health data from a patient's home to clinicians, has promise to alleviate disparities by providing timely access and early intervention, particularly during the COVID-19 pandemic. Studies of digital interventions in oncology have demonstrated reduction in symptom distress and unplanned hospitalizations but lack focus on minority patients whereas studies of telehealth aiming to address disparities have not focused on patients with cancer. In this pilot study, we aimed to evaluate the feasibility of RPM among patients with cancer at a large urban medical center serving a racially and socioeconomically diverse population. Methods: We partnered with a secure HIPAA-compliant platform and FDA-approved RPM device, Current Health, which monitored heart rate, temperature, respiration, oxygen saturation, and blood pressure. The kit included broadband access and a tablet to provide telehealth services. Oncology Clinicians determined clinical inclusion and exclusion criteria of RPM initiation for patients on the bone marrow transplant service and patients with myeloma and lung cancer. A centralized team of Nurse Practitioners (NPs) monitored alarms. Clinical alarms indicated abnormal vital signs;technical alarms indicated no data transmission for a 12-hour period. We measured feasibility by recruitment and retention, and used descriptive statistics to describe the study population, time enrolled on RPM, and alarms. Results: To date, we enrolled 30 patients on the RPM platform over a 10-month period with a weekly census of 9-10 patients undergoing RPM monitoring. Of the 30 patients, 17 (57%) were white, 7 (23%) Black, and 2 (7%) Asian;2 patients (7%) identified as Hispanic. The average age was 57.4 years. The majority of patients (93%) had hematologic malignancies, all of whom were enrolled on hospital discharge. Of the 2 patients with lung cancer, 1 patient was enrolled from the outpatient setting and 1 following hospital discharge. The mean length of time per patient enrolled with the device was 21.7 days. Over 10 months, there were 393 technical and 62 clinical alarms with an average of 3 clinical alarms per week addressed by NPs by phone, indicating low clinician burden. Conclusions: This pilot study demonstrated the feasibility of RPM monitoring in patients with cancer. Future studies should evaluate patient-reported and healthcare utilization outcomes, as well as barriers to reimbursement. The identification of best practices in telemedicine implementation can accelerate adoption and increase high quality, timely, and equitable cancer care.
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Rationale: SARS-CoV-2 infection has been recognised to cause endotheliitis and a pro-thrombotic state during acute illness. Following acute infection, a phenomenon described as 'Long COVID' can cause persisting morbidity with multiple symptoms including exercise intolerance. In recent months preliminary data has proposed persistence of micro-clots as a mechanism for Long COVID. We sought to further understand if a thromboinflammatory processes could be contributing to clinical phenotypes in patients assessed in a UK Post COVID service. Methods: Retrospective analysis of real-world electronic health data relating to patients attending between May 2020 and Jan 2022 (both post hospital and community managed). D-dimer levels, Von Willebrand Factor antigen (vWFAg), date of acute COVID infection and attendance source were available in 1607 patients (1163 community managed and 444 post hospitalisation with acute SARS-CoV-2). vWFAg: ADAMTS13 ratio was reviewed in a subset of 329 patients and correlated with symptoms and functional assessments such as the 6 minute walk test and/or 1 minute sit-tostand test. vWF(Ag):ADAMTS13 ratio was also calculated on 50 voluntary normal controls (Medical Research Ethics Committee Numbers 08/H0810/54 and 08/H0716/72). Results: In the overall cohort D-dimer and vWF(Ag) levels were mostly in the normal range. However, in post-hospitalised patients 21/90 (23.3%) and 65/500(11.5%) community-managed patients had a D-dimer > 550mg/L more than 180 days from acute infection (figure 1). vWF(Ag) levels showed a similar spectrum of abnormalities. In the subgroup with vWF(Ag):ADAMTS13 ratios analysis, 70 (21%) had evidence of abnormal exercise testing as confirmed by desaturation ≥3% and/or an increase in lactate levels >1 above baseline. 43 (61%) of this group had elevated vWF(Ag):ADAMTS13 >1.5. Abnormal exercise testing was associated with a higher vWF(Ag):ADAMTS13 with a median of 1.5 (IQR 1.2-1.7) compared with 1.2 (IQR 0.9-1.4) in those with normal exercise test (p<0.0001), OR 4.955 [2.850-8.612], p<0.0001). Conclusions: This cohort of patients demonstrates a subgroup with persistently elevated D-dimer and vWFAg levels suggesting these markers of thromboinflammatory processes could be of relevance in defining phenotypes within long COVID. The spectrum of abnormality seen, together with the observed correlation of vWF(Ag): ADAMTS13 ratios with impaired exercise tolerance warrants further evaluation of microvascular/ endothelial dysfunction as a mechanism in Long COVID. Further mechanistic studies are in progress.
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BACKGROUND: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct. PATIENTS AND METHODS: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations. RESULTS: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded. CONCLUSIONS: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial.
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COVID-19 , Neoplasms , COVID-19/epidemiology , Humans , Medical Oncology , Neoplasms/epidemiology , Neoplasms/therapy , Pandemics , Prospective StudiesABSTRACT
Introduction: Patients with thoracic malignancies are susceptible to severe outcomes from coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the disruption to care of patients with thoracic malignancies during the COVID-19 pandemic. Methods: The COVID-19 and Cancer Outcomes Study (CCOS) is a multicenter prospective cohort study comprised of adult patients with a current or past history of hematological malignancy or invasive solid tumor who had an outpatient medical oncology visit on the index week between March 2 and March 6, 2020 at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai in New York, NY (MSSM) or the Dana-Farber Cancer Institute in Boston, MA (DFCI). An electronic data capture platform was used to collect patient-, cancer-, and treatment-related variables during the three months prior to the index week (the baseline period) and the following three months (the pandemic period). Two-by-three contingency tables with Fisher's exact tests were computed. All tests were two-tailed and considered statistically significant for p<0.05. All analyses were done in the R statistical environment (v3.6.1). Results: The overall cohort included 2365 patients, of which 313 had thoracic malignancies, 1578 had other solid tumors, and 474 had hematological malignancies. At a median follow-up of 84 days (95% confidence interval, 82-84), 13 patients with thoracic malignancies (4.1%) had developed COVID-19 (vs. other solid: 63 [4.0%] and hematological: 52 [11.0%];p<0.001). When comparing data from the pandemic period to the baseline period, patients with thoracic malignancies had a decrease in the number of in-person outpatient visits (thoracic: 209 [66.8%] vs. other solid: 749 [47.5%] vs. hematological: 260 [54.9%];p<0.001) and an increase in the number of telehealth visits (thoracic: 126 [40.3%] vs. other solid: 465 [29.5%] vs. hematological: 168 [35.4%];p<0.001). During the pandemic period, 33 (10.5%) patients with thoracic malignancies experienced treatment delays due to the pandemic (vs. other solid: 127 [8.0%] and hematological: 79 [16.7%];p<0.001), and 26 (8.3%) patients with thoracic malignancies experienced delays in cancer imaging or diagnostic procedures (vs. other solid: 63 [4.0%] and hematological: 26 [5.5%];p=0.003). Discussion: In this prospective cohort study, patients with thoracic malignancies were not at increased risk of developing COVID-19 compared to patients with other cancers, but experienced significant cancer care disruption during the COVID-19 pandemic with a higher likelihood of decreased in-person visits and increased telehealth visits compared to patients with other malignancies. Focused efforts to ensure continuity of care for this vulnerable patient population are warranted.
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BACKGROUND: The COVID-19 pandemic substantially impacted care of patients with schizophrenia treated with long-acting injectable antipsychotics (LAIs). This study examined how clinics adapted operations to maintain a standard of care for these patients after pandemic onset. METHODS: Online surveys were completed in October-November 2020 by one principal investigator (PI) or PI-appointed designee at 35 clinics participating in OASIS (NCT03919994). Items concerned pandemic impacts on clinic operations, particularly telepsychiatry, and on the care of patients with schizophrenia treated with LAIs. RESULTS: All 35 clinics reported using telepsychiatry;20 (57%) implemented telepsychiatry after pandemic onset. Telepsychiatry visits increased from 12%-15% to 45%-69% across outpatient visit types after pandemic onset;frequency of no-show and/or canceled telepsychiatry visits decreased by approximately one-third. Nearly half of clinics increased the frequency of telepsychiatry visits for patients with schizophrenia treated with LAIs. Approximately one-third of participants each reported switching patients treated with LAIs to longer injection interval LAIs or to oral antipsychotics. The most common system/clinic- and patient-related barrier for telepsychiatry visits was lower reimbursement rate and access to technology/reliable internet, respectively. Almost all participants (94%) were satisfied with telepsychiatry for maintaining care of patients with schizophrenia treated with LAIs;most predicted a hybrid of telepsychiatry and office visits post-pandemic. CONCLUSIONS: Changes made by clinics after pandemic onset were viewed by almost all participants as satisfactory for maintaining a standard of care for patients with schizophrenia treated with LAIs. Most participants predicted continuing telepsychiatry to support patient care post-pandemic;equitable access to telepsychiatry will be important in this regard. FUNDING: Alkermes, Inc.
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Background and aims: Hereditary transthyretin amyloidosis (hATTR) is a rare, progressive, systemic, fatal condition in which misfolded transthyretin proteins form amyloid in tissues and organs, often manifesting in polyneuropathy (hATTR-PN). The FDA has approved 2 gene-silencing pharmacotherapies for hATTR-PN: inotersen, administered subcutaneously;and patisiran, administered intravenously. Patient satisfaction for each treatment was examined during a period overlapping with the COVID-19 pandemic. Methods: Patients with hATTR-PN (with and without accompanying cardiomyopathy) in the United States participated in an observational, online survey between January 1 and October 25, 2020. The Treatment Satisfaction Questionnaire for Medication, version II (TSQMvII), was administered to 29 patients currently being treated with inotersen (n = 11) or patisiran (n = 18). TSQMvII produces 4 scale scores—Effectiveness, Side Effects, Convenience, and Global Satisfaction—ranging from 0 to 100. Higher scores indicate greater satisfaction. TSQMvII scores were descriptively compared between treatment groups. Results: Patients receiving inotersen indicated greater satisfaction with convenience than patients receiving patisiran (mean, 76.3 [SD = 19.4] vs 58.6 [15.3], respectively), and less dissatisfaction with treatment side effects (86.1 [16.4] vs 68.3 [19.0]). Ratings were comparable between treatments with respect to effectiveness (72.0 [21.5] vs 67.1 [19.7]) and global satisfaction (78.0 [20.0] vs 74.5 [21.7]). Conclusions: While inotersen and patisiran were rated similarly in effectiveness and overall treatment satisfaction, inotersen was associated with less dissatisfaction with side effects and greater convenience, with the latter possibly reflecting differences in mode of administration (ie, at home vs visit to a clinical site), which may be particularly important during a pandemic.
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Background and aims: Hereditary transthyretin amyloidosis (ATTRv) is a rare, progressive, systemic, fatal condition in which misfolded transthyretin proteins form amyloid in tissues and organs, often manifesting in polyneuropathy (ATTRv-PN). The FDA has approved two gene-silencing pharmacotherapies for ATTRv-PN: inotersen, administered subcutaneously;and patisiran, administered intravenously. Patient satisfaction for each treatment was examined during a period overlapping with the COVID-19 pandemic. Methods: Patients with ATTRv-PN (with and without accompanying cardiomyopathy) in the United States participated in an observational, online survey between January 1st and October 25th 2020. The Treatment Satisfaction Questionnaire for Medication, version II (TSQMvII) was administered to 29 patients currently treated with inotersen (n=11) or patisiran (n=19). TSQMvII produces four scale scores- Effectiveness, Side Effects, Convenience, and Global Satisfaction- ranging from 0 to 100. Higher scores indicate greater satisfaction. TSQMvII scores were descriptively compared between treatment groups. Results: Patients receiving inotersen indicated greater satisfaction with convenience than patients receiving patisiran (means 76.3 [standard deviation=19.4] vs. 58.6 [15.3], respectively), and less dissatisfaction with treatment side effects (86.1 [16.4] vs. 68.3 [19.0]). Ratings were comparable between treatments with respect to effectiveness (72.0 [21.5] vs. 67.1 [19.7]) and global satisfaction (78.0 [20.0] vs. 74.5 [21.7]). Conclusion: While inotersen and patisiran were rated similarly in effectiveness and overall treatment satisfaction, inotersen was associated with less dissatisfaction of side effects, and greater convenience, with the latter possibly reflecting differences in mode of administration (i.e., at home vs. visit to a clinical site), which may be particularly important during a pandemic.
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Background: The COVID-19 pandemic has rapidly altered cancer care. However, the ways in which it has done so and the associated impact at the individual and societal levels remains poorly defined. Methods: CCOS is a multicenter prospective cohort study designed to define the impact of the pandemic on cancer care delivery and outcomes. The CCOS cohort comprised consecutive outpatients with cancer seen at two US cancer centers from March 2 to March 6, 2020 (index visit). Data was collected at baseline, retrospectively from the preceding 3 months, and prospectively at 3-month follow up. Per patient changes in numbers of visits were compared using Wilcoxon signed rank tests. Correlates of increases in telehealth visits and decreases in in-person visits were evaluated using multivariable logistic regression models. Adjusted Odds ratios [aOR] and 95% confidence intervals (CI) were reported. Results: Of 2365 included patients, 1219 (51.6%) had a decrease in in-person visit frequency during the pandemic period relative to the preceding 3 months. Conversely, 760 (32.2%) had an increased frequency of telehealth visits (decrease in in-person and increase in telehealth visits;both p<0.01). 128 (5.4%) patients developed COVID-19. Compared to White patients, Black and Hispanic patients were less likely to have telehealth visits, had no significant change in frequency of in-person visits, and were more likely to develop COVID-19 (Table). [Formula presented] Conclusions: Significant disruptions to routine cancer care were observed during the pandemic period relative to the prior 3 months. Racial and ethnic barriers to the adoption of telehealth, and related socioeconomic factors, place these vulnerable populations simultaneously at disproportionate risk for decreased cancer-related visits and COVID infection, thereby exacerbating existing racial and ethnic health disparities. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: D. Doroshow: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen;Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim;Honoraria (self), Advisory/Consultancy: Athenaeum Partners;Honoraria (self), Advisory/Consultancy: Boston Healthcare Associates. A.L. Schmidt: Travel/Accommodation/Expenses: Pfizer;Travel/Accommodation/Expenses: Astellas. Z. Bakouny: Non-remunerated activity/ies: Bristol Myers Squibb;Research grant/Funding (self): Genentech/ImCore. M.M. Awad: Advisory/Consultancy, Research grant/Funding (self): Bristol Myers Squibb;Advisory/Consultancy, Research grant/Funding (self): Lilly;Advisory/Consultancy, Research grant/Funding (self): AstraZeneca;Advisory/Consultancy, Research grant/Funding (self): Genentech;Advisory/Consultancy: Merck;Advisory/Consultancy: Achilles;Advisory/Consultancy: AbbVie. R. Haddad: Advisory/Consultancy, Research grant/Funding (self): Bristol Myers Squibb;Advisory/Consultancy, Research grant/Funding (self): Merck;Advisory/Consultancy, Research grant/Funding (self): Pfizer;Advisory/Consultancy, Research grant/Funding (self): Genentech;Advisory/Consultancy, Research grant/Funding (self): AstraZeneca;Advisory/Consultancy, Research grant/Funding (self): GlaxoSmithKline. M.D. Galsky: Shareholder/Stockholder/Stock options: Rappta Therapeutics;Honoraria (self): BioMotiv;Honoraria (self): Janssen;Honoraria (self): Dendreon;Honoraria (self): Merck;Honoraria (self): GlaxoSmithKline;Honoraria (self): Lilly;Honoraria (self): Astellas Pharma;Honoraria (self): Genentech;Honoraria (self): Bristol-Myers Squibb;Honoraria (self): Novartis;Honoraria (self): Pfizer;Honoraria (self): EMD Serono;Honoraria (self): AstraZeneca;Honoraria (self): Seattle Genetics;Honoraria (self): Incyte;Honoraria (self): Alleron Therapeutics;Honoraria (self): Dracen;Honoraria (self): Inovio Pharmaceuticals;Honoraria (self): NuMab;Honoraria (self): Dragonfly Therapeutics;Honoraria (institution): Janssen Oncology;Honoraria (institution): Dendreon;Honoraria (institution): Novartis;Honoraria (institu ion): Bristol-Myers Squibb;Honoraria (institution): Merck;Honoraria (institution): AstraZeneca;Honoraria (institution): Genentech/Roche. T.K. Choueiri: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Alexion;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bayer;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): BristolMyersSquibb;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Cerulean;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Eisai;Honoraria (self), Research grant/Funding (self): Foundation Medicine;Honoraria (self), Research grant/Funding (self): Exelixis;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Ipsen;Research grant/Funding (self): 16 Tracon;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Genentech;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche;Honoraria (self), Research grant/Funding (self): Roche Products Limited;Honoraria (self), Research grant/Funding (self): Hoffman-LaRoche;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): GlaxoSmithKline;Advisory/Consultancy, Research grant/Funding (self): Lilly;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Merck;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Peloton;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Pfizer;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Prometheus labs;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Corvus;Research grant/Funding (self): Calithera;Research grant/Funding (self): Analysis Group;Honoraria (self), Research grant/Funding (self): Sanofi/Aventis;Research grant/Funding (self): Takeda;Honoraria (self), Advisory/Consultancy: EMD Serono;Honoraria (self), Advisory/Consultancy: UpToDate;Honoraria (self): NCCN;Honoraria (self), Advisory/Consultancy, Dr. Choueiri reports research support from AstraZeneca, Alexion, Bayer, Bristol Myers Squibb/ER Squibb and sons LLC, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Ipsen, 16 Tracon, Genentech, Roche, Roche Products Limited, F. Hoffmann-La Roche, GlaxoSmithKline, Lilly, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Corvus, Calithera, Analysis Group, Sanofi/Aventis, Takeda;Honoraria: AstraZeneca, Alexion, Sanofi/Aventis, Bayer, Bristol Myers-Squibb/ER Squibb and sons LLC, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Genentech, Roche, Roche Products Limited, F. Hoffmann-La Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN, Analysis Group, NCCN, Michael J. Hennessy (MJH) Associates, Inc (Healthcare Communications Company with several brands such as OnClive, PeerView and PER), Research to Practice, L-path, Kidney Cancer Journal, Clinical Care Options, Platform Q, Navinata Healthcare, Harborside Press, American Society of Me: Analysis Group. All other authors have declared no conflicts of interest.