ARCTIC: Durvalumab + tremelimumab and durvalumab monotherapy vs SoC in ≥ 3L advanced NSCLC treatment

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phase i ii study of spartalizumab pdr001 an anti pd1 mab in patients with advanced melanoma or non small cell lung cancer

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Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON).

In the phase 3 POSEIDON study, first-line tremelimumab plus durvalumab and chemotherapy significantly improved overall survival and progression-free survival versus chemotherapy in metastatic non-small-cell lung cancer (NSCLC). We present patient-reported outcomes (PROs). Treatment-naïve patients were randomized 1:1:1 to tremelimumab plus durvalumab and chemotherapy, durvalumab plus chemotherapy, or chemotherapy. PROs (prespecified secondary endpoints) were assessed using the European Organisation for Research and Treatment of Cancer 30-item core quality of life questionnaire version 3 (QLQ-C30) and its 13-item lung cancer module (QLQ-LC13). We analyzed time to deterioration (TTD) of symptoms, functioning, and global health status/quality of life (QoL) from randomization by log-rank test and improvement rates by logistic regression. 972/1013 (96 %) patients randomized completed baseline QLQ-C30 and QLQ-LC13 questionnaires, with scores comparable between treatment arms. Patients receiving tremelimumab plus durvalumab and chemotherapy versus chemotherapy had longer median TTD for all PRO items. Hazard ratios for TTD favored tremelimumab plus durvalumab and chemotherapy for all items except diarrhea; 95 % confidence intervals did not cross 1.0 for global health status/QoL, physical functioning, cognitive functioning, pain, nausea/vomiting, insomnia, constipation, hemoptysis, dyspnea, and pain in other parts. For durvalumab plus chemotherapy, median TTD was longer versus chemotherapy for all items except nausea/vomiting and diarrhea. Hazard ratios favored durvalumab plus chemotherapy for all items except appetite loss; 95 % confidence intervals did not cross 1.0 for global health status/QoL, physical functioning, role functioning, dyspnea, and pain in other parts. For both immunotherapy plus chemotherapy arms, improvement rates in all PRO items were numerically higher versus chemotherapy, with odds ratios > 1. Tremelimumab plus durvalumab and chemotherapy delayed deterioration in symptoms, functioning, and global health status/QoL compared with chemotherapy. Together with significant improvements in survival, these results support tremelimumab plus durvalumab and chemotherapy as a first-line treatment option in metastatic NSCLC

Use of traditional cooking fuels and the risk of young adult cataract in rural Bangladesh: a hospital-based case-control study

<p>Abstract</p> <p>Background</p> <p>This study aimed to investigate the independent relationship between the use of various traditional biomass cooking fuels and the occurrence of cataract in young adults in rural Bangladesh.</p> <p>Methods</p> <p>A hospital-based age- and sex-matched case-control study incorporating two control groups was conducted. Cases were cataract patients aged 18 and 49 years diagnosed on the basis of any opacity of the crystalline lens or its capsule and visual acuity poorer than 6/18 on the Log Mar Visual Acuity Chart in either eye, or who had a pseudophakic lens as a result of cataract surgery within the previous 5 years. Non-eye-disease (NE) controls were selected from patients from ENT or Orthopaedics departments and non-cataract eye-disease (NC) controls from the Ophthalmology department. Data pertaining to history of exposure to various cooking fuels and to established risk factors for cataract were obtained by face-to-face interview and analyzed using conditional logistic regression.</p> <p>Results</p> <p>Clean fuels were used by only 4% of subjects. A majority of males (64-80% depending on group) had never cooked, while the rest had used biomass cooking fuels, mainly wood/dry leaves, with only 6 having used rice straw and/or cow dung. All females of each group had used wood/dry leaves for cooking. Close to half had also used rice straw and/or cow dung. Among females, after controlling for family history of cataract and education and combining the two control groups, case status was shown to be significantly related to lifetime exposure to rice straw, fitted as a trend variable coded as never, ≤ median of all exposed, > median of all exposed (OR = 1.52, 95%CI 1.04-2.22), but not to lifetime exposure to wood/dry leaves. Case status among females showed an inverse association with ever use of cow dung as a cooking fuel (OR 0.43, 95%CI 0.22-0.81).</p> <p>Conclusions</p> <p>In this population, where cooking is almost exclusively done using biomass fuels, cases of young adult cataract among females were more likely to have had an increased lifetime exposure to cooking with rice straw fuel and not to have cooked using cow dung fuel. There is a possibility that these apparent associations could have been the result of uncontrolled founding, for instance by wealth. The nature of the associations, therefore, needs to be further investigated.</p

Effect of household and village characteristics on financial catastrophe and impoverishment due to health care spending in Western and Central Rural China: A multilevel analysis

<p>Abstract</p> <p>Objective</p> <p>The study aimed to examine the effect of household and community characteristics on financial catastrophe and impoverishment due to health payment in Western and Central Rural China.</p> <p>Methods</p> <p>A household survey was conducted in 2008 in Hebei and Shaanxi provinces and the Inner Mongolia Autonomous Region using a multi-stage sampling technique. Independent variables included village characteristics, household income, chronic illness status, health care use and health spending. A composite contextual variable, named village deprivation, was derived from socio-economic status and availability of health care facilities in each village using factor analysis. Dependent variables were whether household health payment was more than 40% of household's capacity to pay (catastrophic health payment) and whether household per capita income was put under Chinese national poverty line (1067 Yuan income per year) after health spending (impoverishment). Mixed effects logistic regression was used to assess the effect of the independent variables on the two outcomes.</p> <p>Results</p> <p>Households with low per capita income, having elderly, hospitalized or chronically ill members, and whose head was unemployed were more likely to incur financial catastrophe and impoverishment due to health expenditure. Both catastrophic and impoverishing health payments increased with increased village deprivation. However, the presence of a village health clinic had no effect on the two outcomes, nor did household enrollment in the New Rural Cooperative Medical Scheme (national health insurance).</p> <p>Conclusions</p> <p>Village deprivation independently increases the risk for financial hardship due to health payment after adjusting for known household-level factors. This suggests that policy makers need to view the individual, household and village as separate units for policy targeting.</p

WT1 gene expression as a prognostic marker in advanced serous epithelial ovarian carcinoma: an immunohistochemical study

BACKGROUND: WT1 is a tumor suppressor gene responsible for Wilms' tumor. WT1 reactivity is limited to ovarian serous carcinomas. Recent studies have shown that WT1 plays an important role in the progression of disease and indicates a poorer prognosis of human malignancies such as acute myeloid leukemia and breast cancer. The aims of this study were to determine the survival and recurrence-free survival of women with advanced serous epithelial ovarian carcinoma in relation to WT1 gene expression. METHODS: The study accrued women over an 18-year period, from 1987–2004. During the study period, 163 patients were diagnosed with advanced serous epithelial ovarian carcinoma and had undergone complete post-operative chemotherapy, but the final study group comprised 99 patients. The records of these women were reviewed and the paraffin-embedded tissue of these women stained with WT1 immunostaining. Survival analysis was performed using Kaplan-Meier and Cox regression methods. RESULTS: Fifty patients showed WT1 staining and forty-nine did not. Five-year survival of non-staining and staining groups were 39.4% and 10.7% (p < 0.00005); five-year recurrence-free survival of these groups were 29.8% and ≤ 7.5% (p < 0.00005), respectively. For survival the HR of WT1 staining, adjusted for residual tumor and chemotherapy response, was 1.98 (95% CI 1.28–3.79), and for recurrence-free survival the HR was 3.36 (95% CI 1.60–7.03). The HR for recurrence-free survival was not confounded by any other variables. CONCLUSION: This study suggests that expression of WT1 gene may be indicative of an unfavorable prognosis in patients with advanced serous epithelial ovarian carcinoma

The histology of ovarian cancer: worldwide distribution and implications for international survival comparisons (CONCORD-2)

Objective Ovarian cancers comprise several histologically distinct tumour groups with widely different prognosis. We aimed to describe the worldwide distribution of ovarian cancer histology and to understand what role this may play in international variation in survival. Methods The CONCORD programme is the largest population-based study of global trends in cancer survival. Data on 681,759 women diagnosed during 1995â\u80\u932009 with cancer of the ovary, fallopian tube, peritoneum and retroperitonum in 51 countries were included. We categorised ovarian tumours into six histological groups, and explored the worldwide distribution of histology. Results During 2005â\u80\u932009, type II epithelial tumours were the most common. The proportion was much higher in Oceania (73.1%), North America (73.0%) and Europe (72.6%) than in Central and South America (65.7%) and Asia (56.1%). By contrast, type I epithelial tumours were more common in Asia (32.5%), compared with only 19.4% in North America. From 1995 to 2009, the proportion of type II epithelial tumours increased from 68.6% to 71.1%, while the proportion of type I epithelial tumours fell from 23.8% to 21.2%. The proportions of germ cell tumours, sex cord-stromal tumours, other specific non-epithelial tumours and tumours of non-specific morphology all remained stable over time. Conclusions The distribution of ovarian cancer histology varies widely worldwide. Type I epithelial, germ cell and sex cord-stromal tumours are generally associated with higher survival than type II tumours, so the proportion of these tumours may influence survival estimates for all ovarian cancers combined. The distribution of histological groups should be considered when comparing survival between countries and regions

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems