The purpose of this analysis is to evaluate the effect of institutional accrual volume on clinical outcomes among patients receiving chemoradiation for locally advanced non-small cell lung cancer ...(LA-NSCLC) on a phase III trial.
Patients with LA-NSCLC were randomly assigned to 60 Gy or 74 Gy radiotherapy (RT) with concurrent carboplatin/paclitaxel +/- cetuximab on NRG Oncology RTOG 0617. Participating institutions were categorized as low-volume centers (LVCs) or high-volume centers (HVCs) according to the number of patients accrued (≤3 vs > 3). All statistical tests were two-sided.
Range of accrual for LVCs (n = 195) vs HVCs (n = 300) was 1 to 3 vs 4 to 18 patients. Baseline characteristics were similar between the two cohorts. Treatment at a HVC was associated with statistically significantly longer overall survival (OS) and progression-free survival (PFS) compared with treatment at a LVC (median OS = 26.2 vs 19.8 months; HR = 0.70, 95% CI = 0.56 to 0.88, P = .002; median PFS: 11.4 vs 9.7 months, HR = 0.80, 95% CI = 0.65-0.99, P = .04). Patients treated at HVCs were more often treated with intensity-modulated RT (54.0% vs 39.5%, P = .002), had a lower esophageal dose (mean = 26.1 vs 28.0 Gy, P = .03), and had a lower heart dose (median = V5 Gy 38.2% vs 54.1%, P = .006; V50 Gy 3.6% vs 7.3%, P < .001). Grade 5 adverse events (AEs) (5.3% vs 9.2%, P = .09) and RT termination because of AEs (1.3% vs 4.1%, P = .07) were less common among patients treated at HVCs. HVC remained independently associated with longer OS (P = .03) when accounting for other factors.
Treatment at institutions with higher clinical trial accrual volume is associated with longer OS among patients with LA-NSCLC participating in a phase III trial.
A message from ASCO'S President. It has been forty years since President Richard Nixon signed the National Cancer Act of 1971, which many view as the nation's declaration of the "War on Cancer." The ...bill has led to major investments in cancer research and significant increases in cancer survival. Today, two-thirds of patients survive at least five years after being diagnosed with cancer compared with just half of all diagnosed patients surviving five years after diagnosis in 1975. The research advances detailed in this year's Clinical Cancer Advances demonstrate that improvements in cancer screening, treatment, and prevention save and improve lives. But although much progress has been made, cancer remains one of the world's most serious health problems. In the United States, the disease is expected to become the nation's leading cause of death in the years ahead as our population ages. I believe we can accelerate the pace of progress, provided that everyone involved in cancer care works together to achieve this goal. It is this viewpoint that has shaped the theme for my presidential term: Collaborating to Conquer Cancer. In practice, this means that physicians and researchers must learn from every patient's experience, ensure greater collaboration between members of a patient's medical team, and involve more patients in the search for cures through clinical trials. Cancer advocates, insurers, and government agencies also have important roles to play. Today, we have an incredible opportunity to improve the quality of cancer care by drawing lessons from the real-world experiences of patients. The American Society of Clinical Oncology (ASCO) is taking the lead in this area, in part through innovative use of health information technology. In addition to our existing quality initiatives, ASCO is working with partners to develop a comprehensive rapid-learning system for cancer care. When complete, this system will provide physicians with personalized, real-time information that can inform the care of every patient with cancer as well as connect patients with their entire medical teams. The rapid learning system will form a continuous cycle of learning: securely capturing data from every patient at the point of care, drawing on evidence-based guidelines, and evaluating quality of care against those standards and the outcomes of other patients. Clinical trials are another area in which collaboration is critical. Increasing clinical trial participation will require commitment across the cancer community from physicians, patients, insurers, hospitals, and industry. A 2010 report by the Institute of Medicine described challenges to participation in trials by both physicians and patients and provided recommendations for revitalizing clinical trials conducted through the National Cancer Institute's Cooperative Group Program. ASCO has pledged its support for the full implementation of these recommendations. More broadly, ASCO recently outlined a bold vision for translational and clinical cancer research for the next decade and made recommendations to achieve that vision. Accelerating Progress Against Cancer: ASCO's Blueprint for Transforming Clinical and Translational Research, released in November, calls for a research system that takes full advantage of today's scientific and technologic opportunities and sets a high-level agenda for policy makers, regulators, and advocates. Cancer research has transformed cancer care in the past forty years, and this year's Clinical Cancer Advances illustrates how far we have come in the past year alone. We now have a tremendous opportunity to use today's knowledge and collaborate across all facets of cancer care to conquer this deadly disease. Michael P. Link, MD President American Society of Clinical Oncology.
A MESSAGE FROM ASCO'S PRESIDENT
Like many health professionals who care for people with cancer, I entered the field because of specific patients who touched my heart. They still do. In an effort to ...weave together my personal view of what the American Society of Clinical Oncology (ASCO) stands for and the purpose the organization serves, my presidential theme this year is “Patients. Pathways. Progress.” Patients come first. Caring for patients is the most important, rewarding aspect of being an oncology professional. At its best, the relationship between doctor and patient is compassionate and honest—and a relationship of mutual respect. Many professional organizations have an interest in cancer, but no other society is so focused on the entire spectrum of cancer care, education, and research. Nor is any other society as particularly interested in bringing new treatments to our patients through clinical trials as ASCO is. Clinical trials are the crux for improving treatments for people with cancer and are critical for continued progress against the disease. “Pathways” has several meanings. Some pathways are molecular—like the cancer cell's machinery of destruction, which we have only begun to understand in recent years. But there are other equally important pathways, including the pathways new therapies follow as they move from bench to bedside and the pathways patients follow during the course of their diseases. Improved understanding of these pathways will lead to new approaches in cancer care, allowing doctors to provide targeted therapies that deliver improved, personalized treatment. The best pathway for patients to gain access to new therapies is through clinical trials. Trials conducted by the National Cancer Institute's Cooperative Group Program, a nationwide network of cancer centers and physicians, represent the United States' most important pathway for accelerating progress against cancer. This year, the Institute of Medicine released a report on major challenges facing the Cooperative Group Program. Chief among them is the fact that funding for the program has been nearly flat since 2002. ASCO has called for a doubling of funding for cooperative group research within five years and supports the full implementation of the Institute of Medicine recommendations to revitalize the program. ASCO harnesses the expertise and resources of its 28,000 members to bring all of these pathways together for the greater good of patients. Progress against cancer is being made every day—measurable both in our improved understanding of the disease and in our ability to treat it. A report issued in December 2009 by the National Cancer Institute, the Centers for Disease Control and Prevention, the American Cancer Society, and the North American Association of Central Cancer Registries found that rates of new diagnoses and rates of death resulting from all cancers combined have declined significantly in recent years for men and women overall and for most racial and ethnic populations in the United States. The pace of progress can be and needs to be hastened. Much remains to be done. Sustained national investment in cancer research is needed to bring better, more effective, less toxic treatments to people living with cancer. Pathways to progress continue in the clinic as doctors strive to find the right treatments for the right patients, to understand what represents the right treatments, and to partner with patients and caregivers for access to those treatments. This report demonstrates that significant progress is being made on the front lines of clinical cancer research. But although our nation's investment in this research is paying off, we must never forget the magnitude of what lies ahead. Cancer remains the number two killer of Americans. Future progress depends on continued commitment, from both ASCO and the larger medical community. George W. Sledge Jr, MD President American Society of Clinical Oncology
1. Many grasslands in north-west Europe are productive but species-poor communities resulting from intensive agriculture. Reducing the intensity of management under agri-environment schemes has often ...failed to increase botanical diversity. We investigated biotic and abiotic constraints on diversification by manipulating seed and microsite availability, soil fertility, resource competition, herbivory and deficiencies in the soil microbial community. 2. The effectiveness of 13 restoration treatments was investigated over 4 years in a randomized block experiment established in two productive grasslands in central-east and south-west England. 3. Severe disturbance involving turf removal followed by seed addition was the most effective and reliable means of increasing grassland diversity. Disturbance by multiple harrowing was moderately effective but was enhanced by molluscicide application to reduce seedling herbivory and by sowing the hemiparasite Rhinanthus to reduce competition from grasses. 4. Low-level disturbance by grazing or slot-seeding was ineffective in increasing diversity. Inoculation with soil microbial communities from species-rich grasslands had no effect on botanical diversity. Nitrogen and potassium fertilizer addition accelerated off-take of phosphorus in cut herbage but did not cause a reduction in soil phosphorus or increase botanical diversity. 5. Different grazing management regimes had little impact on diversity. This may reflect the constraining effect of the July hay cut on species dispersal and colonization. 6. Synthesis and applications. Three alternative approaches to grassland diversification, with different outcomes, are recommended. (i) High intervention deturfing, which would create patches with low competitive conditions for rapid and reliable establishment of the target community. For reasons of cost and practicality this can only be done over small areas but will form source populations for subsequent spread. (ii) Moderate intervention (harrowing or slot-seeding) over large areas, which would establish a limited number of desirable, generalist species that perform well in restoration. This method is low cost and rapid but the increases in biodiversity are less predictable. (iii) Phased restoration, which would complement the above approaches. Productivity and competition are reduced over 3-5 years using Rhinanthus or fertilizers to accelerate phosphorus off-take. After this time harrowing and seeding should allow a wide range of more specialist species to establish. However, further research is required to determine the long-term effectiveness of these approaches.
1. Declines in area and quality of species-rich mesotrophic and calcareous grasslands have occurred all across Europe. While the European Union has promoted schemes to restore these grasslands, the ...emphasis for management has remained largely focused on plants. Here we focus on restoration of the phytophagous beetles of these grasslands. Although local management, particularly that which promotes the establishment of host plants, is key to restoration success, dispersal limitation is also likely to be an important limiting factor during the restoration of phytophagous beetle assemblages. 2. Using a 3-year multi-site experiment, we investigated how restoration success of phytophagous beetles was affected by hay-spreading management (intended to introduce target plant species), success in restoration of the plant communities and the landscape context within which restoration was attempted. 3. Restoration success of the plants was greatest where green hay spreading had been used to introduce seeds into restoration sites. Beetle restoration success increased over time, although hayspreading had no direct effect. However, restoration success of the beetles was positively correlated with restoration success of the plants. 4. Overall restoration success of the phytophagous beetles was positively correlated with the proportion of species-rich grassland in the landscape, as was the restoration success of the polyphagous beetles. Restoration success for beetles capable of flight and those showing oligophagous host plant specialism were also positively correlated with connectivity to species-rich grasslands. There was no indication that beetles not capable of flight showed greater dependence on landscape scale factors than flying species. 5. Synthesis and applications. Increasing the similarity of the plant community at restoration sites to target species-rich grasslands will promote restoration success for the phytophagous beetles.However, landscape context is also important, with restoration being approximately twice as successful in those landscapes containing high as opposed to low proportions of species-rich grassland.By targeting grassland restoration within landscapes containing high proportions of species-rich grassland, dispersal limitation problems associated with restoration for invertebrate assemblages are more likely to be overcome.
Due to their confinement to specific hostplants or restricted habitat types, Auchenorrhyncha have the potential to make suitable biological indicators to measure the quality of chalk grassland under ...different management practices for nature conservation. The Auchenorrhyncha data from a study designed to identify the factors influencing the invertebrate diversity of chalk grasslands in southern England was used to evaluate the potential use of this group of insects as biological indicators. Between 1998 and 2002 altogether 81 chalk grassland sites were sampled. Vegetation structure and composition were recorded, and Auchenorrhyncha were sampled at each site on three occasions in each of two seasons using a 'Vortis' suction sampler. Auchenorrhyncha assemblages were then linked to the different grassland plant communities occurring on chalk soils according to the British National Vegetation Classification (NVC). Altogether 96 Auchenorrhyncha species were recorded during the study. Using data on the frequency and dominance of species, as is commonly done for plant communities, it was possible to identify the preferential and differential species of distinct Auchenorrhyncha assemblages. Significant differences between the Auchenorrhyncha assemblages associated with the various chalk grassland plant communities of the NVC were observed down to a level of sub-communities. We conclude that data on Auchenorrhyncha assemblages can provide valuable information for the setting of conservation management priorities, where data on floristic composition alone may not be sufficient, providing additional information on aspects of vegetation structure and condition.PUBLICATION ABSTRACT
Treatment of advanced stage non-small cell lung cancer (NSCLC) has changed dramatically due to immunotherapy. However, patients without Programmed Death-Ligand 1 (PD-L1) protein expression often ...benefit less from immunotherapy. This trial is designed to test if stereotactic body radiation therapy (SBRT) to a single tumor site can significantly enhance the outcome of patients with advanced stage PD-L1(-) NSCLC when added to systemic therapy including immunotherapy.
Alliance A082002 is based on subgroup analysis from the randomized phase II PEMBRO-RT trial., PEMBRO-RT compared pembrolizumab alone or with SBRT and revealed improved progression-free and overall survival (PFS and OS, respectively) in PD-L1(-) patients when adding SBRT (8 Gy x 3 fractions). In A082002, patients without PD-L1 expression will be randomized to SBRT (8 Gy x3) plus systemic therapy vs. systemic therapy alone. The primary endpoint of the phase II portion of the trial is PFS and will require 100 patients. The primary endpoint of the phase III portion of the trial is OS and will require an additional 284 patients. This trial will clarify whether adding SBRT to systemic therapy can improve PFS and OS in a larger multi-institutional cohort. Several systemic treatment options are allowed including either immunotherapy alone or chemo-immunotherapy.
This phase II/III Alliance trial A082002 will test whether the addition of SBRT to a single tumor site will enhance the anti-tumor activity of systemic immunotherapy or chemo-immunotherapy in patients with stage IV PD-L1(-) NSCLC. It is now open in the National Clinical Trials Network (NCTN).
Climate change due to greenhouse gas emissions is predicted to raise the mean global temperature by 1.0-3.5°C in the next 50-100 years. The direct and indirect effects of this potential increase in ...temperature on terrestrial ecosystems and ecosystem processes are likely to be complex and highly varied in time and space. The Global Change and Terrestrial Ecosystems core project of the International Geosphere-Biosphere Programme has recently launched a Network of Ecosystem Warming Studies, the goals of which are to integrate and foster research on ecosystem-level effects of rising temperature. In this paper, we use meta-analysis to synthesize data on the response of soil respiration, net N mineralization, and aboveground plant productivity to experimental ecosystem warming at 32 research sites representing four broadly defined biomes, including high (latitude or altitude) tundra, low tundra, grassland, and forest. Warming methods included electrical heat-resistance ground cables, greenhouses, vented and unvented field chambers, overhead infrared lamps, and passive nighttime warming. Although results from individual sites showed considerable variation in response to warming, results from the meta-analysis showed that, across all sites and years, 2-9 years of experimental warming in the range 0.3-6.0°C significantly increased soil respiration rates by 20% (with a 95% confidence interval of 18-22%), net N mineralization rates by 46% (with a 95% confidence interval of 30-64%), and plant productivity by 19% (with a 95% confidence interval of 15-23%). The response of soil respiration to warming was generally larger in forested ecosystems compared to low tundra and grassland ecosystems, and the response of plant productivity was generally larger in low tundra ecosystems than in forest and grassland ecosystems. With the exception of aboveground plant productivity, which showed a greater positive response to warming in colder ecosystems, the magnitude of the response of these three processes to experimental warming was not generally significantly related to the geographic, climatic, or environmental variables evaluated in this analysis. This underscores the need to understand the relative importance of specific factors (such as temperature, moisture, site quality, vegetation type, successional status, land-use history, etc.) at different spatial and temporal scales, and suggests that we should be cautious in "scaling up" responses from the plot and site level to the landscape and biome level. Overall, ecosystem-warming experiments are shown to provide valuable insights on the response of terrestrial ecosystems to elevated temperature.
...the challenge is only compounded by the fact that only one in four technology positions is filled by women - despite the fact that nearly 87 percent of those queried for the study responded that ...they were concerned or very concerned about the lack of women in the tech workforce. Females face a number of obstacles participating in the tech sector, not least of which is a bias that begins in grade school with a lack of encouragement for girls to embrace STEM fields. Companies can pump up their efforts in encouraging more women to apply for tech jobs, as well as do more outreach in providing appropriate training, networking and mentoring for their female workers, ISACA suggested. The problem begins with the fact that hiring managers often - but not always - hire people like themselves and/or like the previous job holder, says Maxine Holt, principal analyst at the Information Security Forum (ISF). Rinki Sethi, senior director of information security at Palo Alto Networks, cites another survey, "The 2017 Global Information Security Workforce Study: Women in Cybersecurity," from the Executive Women's Forum, which found that women are globally underrepresented in the cybersecurity profession at 11 percent. Rising awareness Domini Clark, principal, executive & technical recruitment, Blackmere Consulting Maxine Holt, principal analyst, Information Security Forum (ISF) Rinki Sethi, senior director, information security, Palo Alto Networks TRANSFORMATION: Begins at home Domini Clark of Blackmere Consulting says companies can better the situation for women in the IT security field: * Create environments...
This study focuses on the restoration of chalk grasslands over a 6-year period and tests the efficacy of two management practices, hay spreading and soil disturbance, in promoting this process for ...phytophagous beetles. Restoration success for the beetles, measured as similarity to target species-rich chalk grassland, was not found to be influenced by either management practice. In contrast, restoration success for the plants did increase in response to hay spreading management. Although the presence of suitable host plants was considered to dictate the earliest point at which phytophagous beetles could successfully colonized, few beetle species colonized as soon as their host plants became established. Morphological characteristics and feeding habits of 27 phytophagous beetle species were therefore tested to identify factors that limited their colonization and persistence. The lag time between host plant establishment and colonization was greatest for flightless beetles. Beetles with foliage-feeding larvae both colonized at slower rates than seed-, stem-, or root-feeding species and persisted within the swards for shorter periods. Although the use of hay spreading may benefit plant communities during chalk grassland restoration, it did not directly benefit phytophagous beetles. Without techniques for overcoming colonization limitation for invertebrate taxa, short-term success of restoration may be limited to the plants only.
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