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- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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- Ring, A., et al.
(författare)
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Bridging The Age Gap: observational cohort study of effects of chemotherapy and trastuzumab on recurrence, survival and quality of life in older women with early breast cancer
- 2021
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 125, s. 209-219
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy. Methods: A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage. Results: Three thousands four hundred sixteen women were recruited from 56 UK centres between 2013 and 2018. Two thousands eight hundred eleven (82%) had surgery. 1520/2811 (54%) had high-risk EBC and 2059/2811 (73%) were fit. Chemotherapy was given to 306/1100 (27.8%) fit patients with high-risk EBC. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio [HR] 0.36 [95% CI 0.19–0.68]) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 [95% CI 0.20–0.92]) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 [95% CI 0.08–0.49];BCSS: HR 0.12 [95% CI 0.03–0.44]).Transient negative quality-of-life impacts were observed. Conclusions: Chemotherapy was associated with reduced risk of metastatic recurrence, but survival benefits were only seen in patients with ER-negative cancer. Quality-of-life impacts were significant but transient. Trial Registration: ISRCTN 46099296. © 2021, The Author(s).
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- Gu, Y, et al.
(författare)
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Quick Hot Shot & Young Surgeon Presentation
- 2015
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Ingår i: Hernia : the journal of hernias and abdominal wall surgery. - 1248-9204. ; 19 Suppl 1, s. S77-84
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Tidskriftsartikel (refereegranskat)
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- Wyld, L., et al.
(författare)
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Bridging the age gap in breast cancer: cluster randomized trial of two decision support interventions for older women with operable breast cancer on quality of life, survival, decision quality, and treatment choices
- 2021
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 108:5, s. 499-510
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Rates of surgery and adjuvant therapy for breast cancer vary widely between breast units. This may contribute to differences in survival. This cluster RCT evaluated the impact of decision support interventions (DESIs) for older women with breast cancer, to ascertain whether DESIs influenced quality of life, survival, decision quality, and treatment choice. METHODS: A multicentre cluster RCT compared the use of two DESIs against usual care in treatment decision-making in older women (aged at least ≥70 years) with breast cancer. Each DESI comprised an online algorithm, booklet, and brief decision aid to inform choices between surgery plus adjuvant endocrine therapy versus primary endocrine therapy, and adjuvant chemotherapy versus no chemotherapy. The primary outcome was quality of life. Secondary outcomes included decision quality measures, survival, and treatment choice. RESULTS: A total of 46 breast units were randomized (21 intervention, 25 usual care), recruiting 1339 women (670 intervention, 669 usual care). There was no significant difference in global quality of life at 6 months after the baseline assessment on intention-to-treat analysis (difference -0.20, 95 per cent confidence interval (C.I.) -2.69 to 2.29; P=0.900). In women offered a choice of primary endocrine therapy versus surgery plus endocrine therapy, knowledge about treatments was greater in the intervention arm (94 versus 74 per cent; P=0.003). Treatment choice was altered, with a primary endocrine therapy rate among women with oestrogen receptor-positive disease of 21.0 per cent in the intervention versus 15.4 per cent in usual-care sites (difference 5.5 (95 per cent C.I. 1.1 to 10.0) per cent; P=0.029). The chemotherapy rate was 10.3 per cent at intervention versus 14.8 per cent at usual-care sites (difference -4.5 (C.I. -8.0 to 0) per cent; P=0.013). Survival was similar in both arms. CONCLUSION: The use of DESIs in older women increases knowledge of breast cancer treatment options, facilitates shared decision-making, and alters treatment selection. Trial registration numbers: EudraCT 2015-004220-61 (https://eudract.ema.europa.eu/), ISRCTN46099296 (http://www.controlled-trials.com). © The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.
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| 9. |
- Wyld, L., et al.
(författare)
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Improving outcomes for women aged 70 years or above with early breast cancer: Research programme including a cluster RCT
- 2022
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Ingår i: Programme Grants for Applied Research. - 2050-4322. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: In breast cancer management, age-related practice variation is widespread, with older women having lower rates of surgery and chemotherapy than younger women, based on the premise of reduced treatment tolerance and benefit. This may contribute to inferior outcomes. There are currently no age-and fitness-stratified guidelines on which to base treatment recommendations. Aim: We aimed to optimise treatment choice and outcomes for older women (aged > 70 years) with operable breast cancer. Objectives: Our objectives were to (1) determine the age, comorbidity, frailty, disease stage and biology thresholds for endocrine therapy alone versus surgery plus adjuvant endocrine therapy, or adjuvant chemotherapy versus no chemotherapy, for older women with breast cancer; (2) optimise survival outcomes for older women by improving the quality of treatment decision-making; (3) develop and evaluate a decision support intervention to enhance shared decision-making; and (4) determine the degree and causes of treatment variation between UK breast units. Design: A prospective cohort study was used to determine age and fitness thresholds for treatment allocation. Mixed-methods research was used to determine the information needs of older women to develop a decision support intervention. A cluster-randomised trial was used to evaluate the impact of this decision support intervention on treatment choices and outcomes. Health economic analysis was used to evaluate the cost-benefit ratio of different treatment strategies according to age and fitness criteria. A mixed-methods study was used to determine the degree and causes of variation in treatment allocation. Main outcome measures: The main outcome measures were enhanced age-and fitness-specific decision support leading to improved quality-of-life outcomes in older women (aged > 70 years) with early breast cancer. Results: (1) Cohort study: The study recruited 3416 UK women aged > 70 years (median age 77 years). Follow-up was 52 months. (a) The surgery plus adjuvant endocrine therapy versus endocrine therapy alone comparison: 2854 out of 3416 (88%) women had oestrogen-receptor-positive breast cancer, 2354 of whom received surgery plus adjuvant endocrine therapy and 500 received endocrine therapy alone. Patients treated with endocrine therapy alone were older and frailer than patients treated with surgery plus adjuvant endocrine therapy. Unmatched overall survival and breast-cancer-specific survival were higher in the surgery plus adjuvant endocrine therapy group (overall survival: Hazard ratio 0.27, 95% confidence interval 0.23 to 0.33; p < 0.001; breast-cancer-specific survival: Hazard ratio 0.41, 95% confidence interval 0.29 to 0.58; p < 0.001) than in the endocrine therapy alone group. In matched analysis, surgery plus adjuvant endocrine therapy was still associated with better overall survival (hazard ratio 0.72, 95% confidence interval 0.53 to 0.98; p = 0.04) than endocrine therapy alone, but not with better breast-cancer-specific survival (hazard ratio 0.74, 95% confidence interval 0.40 to 1.37; p = 0.34) or progression-free-survival (hazard ratio 1.11, 95% confidence interval 0.55 to 2.26; p = 0.78). (b) The adjuvant chemotherapy versus no chemotherapy comparison: 2811 out of 3416 (82%) women received surgery plus adjuvant endocrine therapy, of whom 1520 (54%) had high-recurrence-risk breast cancer [grade 3, node positive, oestrogen receptor negative or human epidermal growth factor receptor-2 positive, or a high Oncotype DX® (Genomic Health, Inc., Redwood City, CA, USA) score of > 25]. In this high-risk population, there were no differences according to adjuvant chemotherapy use in overall survival or breast-cancer-specific survival after propensity matching. Adjuvant chemotherapy was associated with a lower risk of metastatic recurrence than no chemotherapy in the unmatched (adjusted hazard ratio 0.36, 95% confidence interval 0.19 to 0.68; p = 0.002) and propensity-matched patients (adjusted hazard ratio 0.43, 95% confidence interval 0.20 to 0.92; p = 0.03). Adjuva t chemotherapy improved the overall survival and breast-cancer-specific survival of patients with oestrogen-receptor-negative disease. (2) Mixed-methods research to develop a decision support intervention: An iterative process was used to develop two decision support interventions (each comprising a brief decision aid, a booklet and an online tool) specifically for older women facing treatment choices (endocrine therapy alone or surgery plus adjuvant endocrine therapy, and adjuvant chemotherapy or no chemotherapy) using several evidence sources (expert opinion, literature and patient interviews). The online tool was based on models developed using registry data from 23,842 patients and validated on an external data set of 14,526 patients. Mortality rates at 2 and 5 years differed by < 1% between predicted and observed values. (3) Cluster-randomised clinical trial of decision support tools: 46 UK breast units were randomised (intervention, n = 21; usual care, n = 25), recruiting 1339 women (intervention, n = 670; usual care, n = 669). There was no significant difference in global quality of life at 6 months post baseline (difference-0.20, 95% confidence interval-2.7 to 2.3; p = 0.90). In women offered a choice of endocrine therapy alone or surgery plus adjuvant endocrine therapy, knowledge about treatments was greater in the intervention arm than the usual care arm (94% vs. 74%; p = 0.003). Treatment choice was altered, with higher rates of endocrine therapy alone than of surgery in the intervention arm. Similarly, chemotherapy rates were lower in the intervention arm (endocrine therapy alone rate: Intervention sites 21% vs. usual-care sites 15%, difference 5.5%, 95% confidence interval 1.1% to 10.0%; p = 0.02; adjuvant chemotherapy rate: Intervention sites 10% vs. usual-care site 15%, difference 4.5%, 95% confidence interval 0.0% to 8.0%; p = 0.013). Survival was similar in both arms. (4) Health economic analysis: A probabilistic economic model was developed using registry and cohort study data. For most health and fitness strata, surgery plus adjuvant endocrine therapy had lower costs and returned more quality-adjusted life-years than endocrine therapy alone. However, for some women aged > 90 years, surgery plus adjuvant endocrine therapy was no longer cost-effective and generated fewer quality-adjusted life-years than endocrine therapy alone. The incremental benefit of surgery plus adjuvant endocrine therapy reduced with age and comorbidities. (5) Variation in practice: analysis of rates of surgery plus adjuvant endocrine therapy or endocrine therapy alone between the 56 breast units in the cohort study demonstrated significant variation in rates of endocrine therapy alone that persisted after adjustment for age, fitness and stage. Clinician preference was an important determinant of treatment choice. Conclusions: This study demonstrates that, for older women with oestrogen-receptor-positive breast cancer, there is a cohort of women with a life expectancy of < 4 years for whom surgery plus adjuvant endocrine therapy may offer little benefit and simply have a negative impact on quality of life. The Age Gap decision tool may help make this shared decision. Similarly, although adjuvant chemotherapy offers little benefit and has a negative impact on quality of life for the majority of older women with oestrogen-receptor-positive breast cancer, for women with oestrogen-receptor-negative breast cancer, adjuvant chemotherapy is beneficial. The negative impacts of adjuvant chemotherapy on quality of life, although significant, are transient. This implies that, for the majority of fitter women aged > 70 years, standard care should be offered. Limitations: As with any observational study, despite detailed propensity score matching, residual bias cannot be excluded. Follow-up was at median 52 months for the cohort analysis. Longer-term follow-up will be required to validate these findings owing to the slow time course of oestrogen-receptor-positive breast cancer. Future work: The online algorithm is now available (URL: Https://ag gap.shef.ac.uk/; accessed May 2022). There are plans to validate the tool and incorprate quality-of-life and 10-year survival outcomes.
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| 10. |
- Battisti, N. M. L., et al.
(författare)
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Observational cohort study in older women with early breast cancer: Use of radiation therapy and impact on health-related quality of life and mortality
- 2021
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140. ; 161, s. 166-176
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Tidskriftsartikel (refereegranskat)abstract
- Background: Radiotherapy reduces in-breast recurrence risk in early breast cancer (EBC) in older women. This benefit may be small and should be balanced against treatment effect and holistic patient assessment. This study described treatment patterns according to fitness and impact on health-related quality-of-life (HRQoL). Methods: A multicentre, observational study of EBC patients aged ≥ 70 years, undergoing breast-conserving surgery (BCS) or mastectomy, was undertaken. Associations between radiotherapy use, surgery, clinico-pathological parameters, fitness based on geriatric parameters and treatment centre were determined. HRQoL was measured using the European Organisation for the Research and Treatment of Cancer (EORTC) questionnaires. Results: In 2013–2018 2811 women in 56 UK study centres underwent surgery with a median follow-up of 52 months. On multivariable analysis, age and tumour risk predicted radiotherapy use. Among healthier patients (based on geriatric assessments) with high-risk tumours, 534/613 (87.1%) having BCS and 185/341 (54.2%) having mastectomy received radiotherapy. In less fit individuals with low-risk tumours undergoing BCS, 149/207 (72.0%) received radiotherapy. Radiotherapy effects on HRQoL domains, including breast symptoms and fatigue were seen, resolving by 18 months. Conclusion: Radiotherapy use in EBC patients ≥ 70 years is affected by age and recurrence risk, whereas geriatric parameters have limited impact regardless of type of surgery. There was geographical variation in treatment, with some fit older women with high-risk tumours not receiving radiotherapy, and some older, low-risk, EBC patients receiving radiotherapy after BCS despite evidence of limited benefit. The impact on HRQoL is transient. © 2021 Elsevier B.V.
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