Tumour stage, treatment, and survival of women with high-grade serous tubo-ovarian cancer in UKCTOCS: an exploratory analysis of a randomised controlled trial

Background: In UKCTOCS, there was a decrease in the diagnosis of advanced stage tubo-ovarian cancer but no reduction in deaths in the multimodal screening group compared with the no screening group. Therefore, we did exploratory analyses of patients with high-grade serous ovarian cancer to understand the reason for the discrepancy.// Methods: UKCTOCS was a 13-centre randomised controlled trial of screening postmenopausal women from the general population, aged 50–74 years, with intact ovaries. The trial management system randomly allocated (2:1:1) eligible participants (recruited from April 17, 2001, to Sept 29, 2005) in blocks of 32 using computer generated random numbers to no screening or annual screening (multimodal screening or ultrasound screening) until Dec 31, 2011. Follow-up was through national registries until June 30, 2020. An outcome review committee, masked to randomisation group, adjudicated on ovarian cancer diagnosis, histotype, stage, and cause of death. In this study, analyses were intention-to-screen comparisons of women with high-grade serous cancer at censorship (Dec 31, 2014) in multimodal screening versus no screening, using descriptive statistics for stage and treatment endpoints, and the Versatile test for survival from randomisation. This trial is registered with the ISRCTN Registry, 22488978, and ClinicalTrials.gov, NCT00058032.// Findings: 202 562 eligible women were recruited (50 625 multimodal screening; 50 623 ultrasound screening; 101 314 no screening). 259 (0·5%) of 50 625 participants in the multimodal screening group and 520 (0·5%) of 101 314 in the no screening group were diagnosed with high-grade serous cancer. In the multimodal screening group compared with the no screening group, fewer were diagnosed with advanced stage disease (195 [75%] of 259 vs 446 [86%] of 520; p=0·0003), more had primary surgery (158 [61%] vs 219 [42%]; p<0·0001), more had zero residual disease following debulking surgery (119 [46%] vs 157 [30%]; p<0·0001), and more received treatment including both surgery and chemotherapy (192 [74%] vs 331 [64%]; p=0·0032). There was no difference in the first-line combination chemotherapy rate (142 [55%] vs 293 [56%]; p=0·69). Median follow-up from randomisation of 779 women with high-grade serous cancer in the multimodal and no screening groups was 9·51 years (IQR 6·04–13·00). At censorship (June 30, 2020), survival from randomisation was longer in women with high-grade serous cancer in the multimodal screening group than in the no screening group with absolute difference in survival of 6·9% (95% CI 0·4–13·0; p=0·042) at 18 years (21% [95% CI 15·6–26·2] vs 14% [95% CI 10·5–17·4]).// Interpretation: To our knowledge, this is the first evidence that screening can detect high-grade serous cancer earlier and lead to improved short-term treatment outcomes compared with no screening. The potential survival benefit for women with high-grade serous cancer was small, most likely due to only modest gains in early detection and treatment improvement, and tumour biology. The cumulative results of the trial suggest that surrogate endpoints for disease-specific mortality should not currently be used in screening trials for ovarian cancer

Tumour stage, treatment, and survival of women with high-grade serous tubo-ovarian cancer in UKCTOCS: an exploratory analysis of a randomised controlled trial

Background: In UKCTOCS, there was a decrease in the diagnosis of advanced stage tubo-ovarian cancer but no reduction in deaths in the multimodal screening group compared with the no screening group. Therefore, we did exploratory analyses of patients with high-grade serous ovarian cancer to understand the reason for the discrepancy. Methods: UKCTOCS was a 13-centre randomised controlled trial of screening postmenopausal women from the general population, aged 50–74 years, with intact ovaries. The trial management system randomly allocated (2:1:1) eligible participants (recruited from April 17, 2001, to Sept 29, 2005) in blocks of 32 using computer generated random numbers to no screening or annual screening (multimodal screening or ultrasound screening) until Dec 31, 2011. Follow-up was through national registries until June 30, 2020. An outcome review committee, masked to randomisation group, adjudicated on ovarian cancer diagnosis, histotype, stage, and cause of death. In this study, analyses were intention-to-screen comparisons of women with high-grade serous cancer at censorship (Dec 31, 2014) in multimodal screening versus no screening, using descriptive statistics for stage and treatment endpoints, and the Versatile test for survival from randomisation. This trial is registered with the ISRCTN Registry, 22488978, and ClinicalTrials.gov, NCT00058032. Findings: 202 562 eligible women were recruited (50 625 multimodal screening; 50 623 ultrasound screening; 101 314 no screening). 259 (0·5%) of 50 625 participants in the multimodal screening group and 520 (0·5%) of 101 314 in the no screening group were diagnosed with high-grade serous cancer. In the multimodal screening group compared with the no screening group, fewer were diagnosed with advanced stage disease (195 [75%] of 259 vs 446 [86%] of 520; p=0·0003), more had primary surgery (158 [61%] vs 219 [42%]; p<0·0001), more had zero residual disease following debulking surgery (119 [46%] vs 157 [30%]; p<0·0001), and more received treatment including both surgery and chemotherapy (192 [74%] vs 331 [64%]; p=0·0032). There was no difference in the first-line combination chemotherapy rate (142 [55%] vs 293 [56%]; p=0·69). Median follow-up from randomisation of 779 women with high-grade serous cancer in the multimodal and no screening groups was 9·51 years (IQR 6·04–13·00). At censorship (June 30, 2020), survival from randomisation was longer in women with high-grade serous cancer in the multimodal screening group than in the no screening group with absolute difference in survival of 6·9% (95% CI 0·4–13·0; p=0·042) at 18 years (21% [95% CI 15·6–26·2] vs 14% [95% CI 10·5–17·4]). Interpretation: To our knowledge, this is the first evidence that screening can detect high-grade serous cancer earlier and lead to improved short-term treatment outcomes compared with no screening. The potential survival benefit for women with high-grade serous cancer was small, most likely due to only modest gains in early detection and treatment improvement, and tumour biology. The cumulative results of the trial suggest that surrogate endpoints for disease-specific mortality should not currently be used in screening trials for ovarian cancer. Funding: National Institute for Health Research, Medical Research Council, Cancer Research UK, The Eve Appeal

Do agri-environment schemes result in improved water quality?

Welsh Government. Grant Number: 183/2007/0

Five decades' experience of long‐term soil monitoring, and key design principles, to assist the EU soil health mission

The European Union has a long-term objective to achieve healthy soils by 2050. The European Commission has proposed a Directive of the European Parliament and of the Council on Soil Monitoring and Resilience (Soil Monitoring Law, SML), the first stage of which is to focus on setting up a soil monitoring framework and assessing soils throughout the EU. Situated in NW Europe, the UK has substantial experience in soil monitoring over the last half century which may usefully contribute to this wider EU effort. A set of overarching principles have and continue to guide design of national soil monitoring and may prove helpful as other European countries embark on similar monitoring programmes. Therefore, we present the principles of design from five decades of national soil monitoring. The monitoring discussed is based on a stratified-random design, has matured in support of policy questions, and operates over space and time scales relevant to the SML. The UK Centre for Ecology & Hydrology (UKCEH) Countryside Surveys (CS) of Great Britain and Northern Ireland, Welsh Government, Environment and Rural Affairs Monitoring and Modelling Programme (ERAMMP) and the England Ecosystem Survey (EES) monitoring programme are national programmes currently operating in the UK. Some important lessons learnt include: adopting a question-based approach; having a clear robust statistical design for the purpose; selecting indicators that address policy and underlying scientific questions; and selecting indicators that can detect change and use robust and well-tested methodologies across a wide range of soil and land use types, remaining valid over long time scales, supporting thinking long-term. Technical lessons learned include the proven cost effectiveness of a stratified-random design including replication, while adopting a common stratification layer of stable environmental attributes aids comparability between monitoring programmes. Common protocols are vital for future intercomparisons, but a full ecosystem approach that includes co-located soil and vegetation samples for interpreting a co-evolving system has proved hugely advantageous. UK monitoring programmes offer a range of experience that may prove valuable to future soil monitoring design to address the major societal challenges of our time, such as maintaining food production and addressing climate change and biodiversity loss

How hungry are carnivorous plants? An investigation into the nutrition of carnivorous plant taxa from the Kimberley region of Western Australia

Volume: 44Start Page: 207End Page: 21

Combining multiple serum tumor markers improves detection of stage I epithelial ovarian cancer

Objective. Currently available tumor markers for ovarian cancer are still inadequate in both sensitivity and specificity to be used for population-based screening. Artificial neural network (ANN) as a modeling tool has demonstrated its ability to assimilate information from multiple sources and to detect subtle and complex patterns. In this paper, an ANN model was evaluated for its performance in detecting early stage epithelial ovarian cancer using multiple serum markers.Methods. Serum specimens collected at four institutions in the US, the Netherlands and the United Kingdom were analyzed for CA 125II, CA 724, CA 15-3 and macrophage colony stimulating factor (M-CSF). The four tumor marker values were then used as inputs to an ANN derived using a training set from 100 apparently healthy women, 45 women with benign conditions arising from the ovary and 55 invasive epithelial ovarian cancer patients (including 27 stage I/II cases). A separate validation set from 27 apparently healthy women, 56 women with benign conditions and 35 women with various types of malignant pelvic masses was used to monitor the ANN's performance during training. An independent test data set from 98 apparently healthy women and 52 early stage epithelial ovarian cancer patients (38 stage I and 4 stage II invasive cases and 10 stage I borderline ovarian tumor cases) was used to evaluate the ANN.Results. ROC analysis confirmed the overall superiority of the ANN-derived composite index over CA 125II alone (p=0.0333). At a fixed specificity of 98%, the sensitivities for ANN and CA 125II alone were 71% (37/52) and 46% (24/52) (p=0.047), respectively, for detecting early stage epithelial ovarian cancer, and 71% (30/42) and 43% (18/42) (p=0.040), respectively, for detecting invasive early stage epithelial ovarian cancer.Conclusions. The combined use of multiple tumor markers through an ANN improves the overall accuracy to discern healthy women from patients with early stage ovarian cancer. Analysis of multiple markers with an ANN may be a better choice than the use of CA 125II alone in a two-step approach for population screening in which a secondary test such as ultrasound is used to keep the overall specificity at an acceptable level. (C) 2007 Elsevier Inc. All rights reserved