Involvement of low- and middle-income countries in randomized controlled trial publications in oncology

Background: We describe trends in participation by investigators from low- and middle-income countries (LMCs) in publications describing oncology randomized control trials (RCTs) over a decade. Methods: We used Medline to identify RCTs published in English from 1998 to 2008 evaluating treatment in lung, breast, colorectal, stomach and liver cancers. Data on author affiliations, authorship roles, trial characteristics, funding and interventions were extracted from each article. Countries were stratified as low-, middle- or high-income using World Bank data. Interventions were categorized as requiring basic, limited, enhanced or maximal resources as per the Breast Health Global Initiative classification. Logistic regression was used to identify factors associated with authorship by investigators from LMCs. Results: 454 publications were identified. Proportion of articles with at least one LMC author increased over time from 20% in 1998 to 29% in 2008 (p = 0.01), but almost all LMC authors were from middle-income countries. Proportion of articles with at least one LMC author was higher among articles that explicitly reported recruitment in at least one LMC vs those that did not (76% vs 13%). Among 87 articles (19%) that involved authors from LMCs, 17% had LMC authors as first or corresponding authors, and 67% evaluated interventions requiring enhanced or maximal resources. Factors associated with LMC authorship included industry funding (OR = 3.54, p = 0.0001), placebo comparator arm (OR = 2.57, p = 0.02) and palliative intent treatment (OR = 4.00, p = 0.0003). Conclusion: An increasing number of publications describing oncology RCTs involve authors from LMC countries but primarily in non-leadership roles in industry-funded trials

Studi Volume Lalu Lintas di Jalan Raya Narogong Cileungsi, Kabupaten Bogor, Periode Agustus 2011

Survey of traffic volume is one of the simplest methods to obtain traffic data in order to better understand optimalisation andefficiency so that it can minimize vehicle traffic congestion problems on the highway. The method used is based on descriptive andanalytical methods, which is done is to classify the vehicles in classes manually by counting the number of vehicles per time unitbased on class - class. The purpose of the volume of traffic surveys carried out in the classified Narogong Cullinan Road, Bogorregency during the period August, 2011, results that can be found is the degree of saturation of the highway is still in an acceptablelevel. Analysis of traffic flow at the study site is still under the limit congestion. It is suggested that to reduce the traffic density, thetype of heavy vehicles such as out of the factory operates around the study site between the hours of 10:00 pm to 3:00 am

Personhood, belonging, affect and affliction

What does migrancy mean for personhood, and how does this flow through caring relations? Drawing on life history interviews and photo elicitation with 43 people who identify as migrants and live with cancer, here we argue for the significance of recognising complex personhood as it inflects illness and care. Drawing on social science theory around temporalities, moralities and belonging, we assemble a series of cross-cutting themes at the intersection of personhood and care; relations that transcend cultural origins yet are vividly illustrated in relation to migrant pasts. In seeking a multidimensional view of personhood, we attend to the intersecting layers of complexity that make up care in this context vis-a-vis an emphasis on forms of difference, vulnerability and otherness. In this way, we develop an approach to personhood and care that broadens the lens on migrancy and cancer, but also, one that speaks to the importance of recognition of complexity and how it shapes care more generally

Living (well) with cancer in the precision era

Surviving cancer in the precision era of targeted drugs and immunotherapies increasingly involves surviving-with malignancy. Against this backdrop of precision, innovation and chronicity, this paper offers a person-centred examination of some of the emerging intersections of chronic living and cancer treatment. Using a temporally extended qualitative methodology drawing on solicited diaries and successive in-depth interviews with people receiving precision cancer therapies, we focus on the often opaque worlds of surviving-with cancer, day-to-day, amidst the evolving scene of therapeutic innovation. Tracing how elements of the catastrophic and the mundane are braided through these everyday experiences, we seek to provide an embodied and temporally extended account of everyday life, beyond the binaries of presence/absence of disease, or of death/cure. In so doing, we consider how the normative expectations of treatment, bodies, care and emotions are being reshaped, elevating the moral work of the precision-cancer intersection

NUTMEG: A randomized phase II study of nivolumab and temozolomide versus temozolomide alone in newly diagnosed older patients with glioblastoma.

BACKGROUND: There is an immunologic rationale to evaluate immunotherapy in the older glioblastoma population, who have been underrepresented in prior trials. The NUTMEG study evaluated the combination of nivolumab and temozolomide in patients with glioblastoma aged 65 years and older. METHODS: NUTMEG was a multicenter 2:1 randomized phase II trial for patients with newly diagnosed glioblastoma aged 65 years and older. The experimental arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant nivolumab and temozolomide. The standard arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant temozolomide. The primary objective was to improve overall survival (OS) in the experimental arm. RESULTS: A total of 103 participants were randomized, with 69 in the experimental arm and 34 in the standard arm. The median (range) age was 73 (65-88) years. After 37 months of follow-up, the median OS was 11.6 months (95% CI, 9.7-13.4) in the experimental arm and 11.8 months (95% CI, 8.3-14.8) in the standard arm. For the experimental arm relative to the standard arm, the OS hazard ratio was 0.85 (95% CI, 0.54-1.33). In the experimental arm, there were three grade 3 immune-related adverse events which resolved, with no unexpected serious adverse events. CONCLUSIONS: Due to insufficient evidence of benefit with nivolumab, the decision was made not to transition to a phase III trial. No new safety signals were identified with nivolumab. This complements the existing series of immunotherapy trials. Research is needed to identify biomarkers and new strategies including combinations

Alectinib versus crizotinib in untreated ALK-positive non–small-cell lung cancer

Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease. In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival. During a median follow-up of 17.6 months (crizotinib) and 18.6 months (alectinib), an event of disease progression or death occurred in 62 of 152 patients (41%) in the alectinib group and 102 of 151 patients (68%) in the crizotinib group. The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P<0.001); the median progression-free survival with alectinib was not reached. The results for independent review committee-assessed progression-free survival were consistent with those for the primary end point. A total of 18 patients (12%) in the alectinib group had an event of CNS progression, as compared with 68 patients (45%) in the crizotinib group (cause-specific hazard ratio, 0.16; 95% CI, 0.10 to 0.28; P<0.001). A response occurred in 126 patients in the alectinib group (response rate, 82.9%; 95% CI, 76.0 to 88.5) and in 114 patients in the crizotinib group (response rate, 75.5%; 95% CI, 67.8 to 82.1) (P=0.09). Grade 3 to 5 adverse events were less frequent with alectinib (41% vs. 50% with crizotinib). As compared with crizotinib, alectinib showed superior efficacy and lower toxicity in primary treatment of ALK-positive NSCLC. (Funded by F. Hoffmann-La Roche; ALEX ClinicalTrials.gov number, NCT02075840 .)

Routines of isolation? A qualitative study of informal caregiving in the context of glioma in Australia

Informal caregiving for a person living with glioma can be both rewarding and multidimensionally challenging, given the potential for debilitating symptoms, cognitive impairment or personality changes, as early as diagnosis. There is growing evidence that, due to the demands of care, experiences and feelings of loneliness and isolation among informal caregivers are widespread, and opportunities for quality or meaningful social connectedness are lacking. While considerable research has quantified the causes and effects of loneliness and isolation in informal care contexts, the lived experience of loneliness has received relatively little attention. The aim of this study was to better understand the everyday experiences of a group of home-based informal caregivers of people living with glioma in Queensland, Australia. Drawing on in-depth interviews with 32 informal caregivers, purposively sampled, and recruited through a tertiary hospital, in this paper, we explore how the various experiences, demands, and social and relational dynamics in/of informal care (re)produce forms of isolation and loneliness. Using the framework approach to thematic analysis, we derived four themes: (a) the ‘need’ to be near the care recipient, and the implications for caregiver mobility; (b) the strong sense of responsibility for care, and the virtues of ‘good’ caring; (c) experiences of loneliness in the company of others and (d) postponement of social connection and minimising the self. The findings, we argue, are reflective of broader social and moral norms and expectations within experiences of home-based informal care