In order to ensure the provision of goods and services from forests, many governments have promoted less-traditional conservation initiatives such as programs of payments for ecosystem services ...called, more broadly, direct payments for conservation. The Socio Bosque Program (SBP) is a governmental program in Ecuador that directly provides economic incentives to rural families and local and indigenous communities who have voluntarily agreed to comply with some conservation activities. An impact evaluation method (matching) was used to assess the impact of the SBP between 2008 and 2014. This study revealed that on average, the SBP reduced deforestation by 1.5% in those forests that received the SBP's direct payment. These forests would have been deforested if the SBP had not been implemented. Assessment of the impact of the SBP on individual and collective contracts, using the matching method, revealed that 3.4% and roughly 1% of the forest would have been deforested in the absence of the program, respectively. In other words, the protected area in the collective SBP was 1,247,500 ha and, if the SBP had not been implemented, an area of 11,227 ha would have been lost between 2008 and 2014. The 165,700 ha protected by the individual SBP, it was estimated that 5,733 ha were not deforested due to the implementation of the conservation program. Conventional estimates of the impact of the SBP tend to overestimate avoided deforestation because they do not control for observable covariates that correlate with or affect both SBP participation and deforestation. The conclusions are robust, even given potential hidden biases. The present study demonstrated that the SBP serves to mitigate the effects of climate change, especially with those contracts that are intended for individual owners.
Summary Background For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the ...first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. Methods In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12 894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. Findings Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio RR 0·90 95% CI 0·79–1·02 during years 5–9 and 0·75 0·62–0·90 in later years; breast cancer mortality RR 0·97 0·79–1·18 during years 5–9 and 0·71 0·58–0·88 in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12 894 women, mortality without recurrence from causes other than breast cancer was little affected (688 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 0·89–1·10; p=0·78). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 including 0·2% mortality in both treatment groups), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·75 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). Interpretation For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. Funding Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.
Most evaluations of the effectiveness of PAs have relied on indirect estimates based on comparisons between protected and unprotected areas. Such methods can be biased when protection is not randomly ...assigned. We add to the growing literature on the impact of PAs by answering the following research questions: What is the impact of Chilean PAs on deforestation which occurred between 1986 and 2011? How do estimates of the impact of PAs vary when using only public land as control units? We show that the characteristics of the areas in which protected and unprotected lands are located differ significantly. To satisfactorily estimate the effects of PAs, we use matching methods to define adequate control groups, but not as in previous research. We construct control groups using separately non-protected private areas and non-protected public lands. We find that PAs avoid deforestation when using unprotected private lands as valid controls, however results show no impact when the control group is based only on unprotected public land. Different land management regimes, and higher levels of enforcement inside public lands may reduce the opportunity to add additional conservation benefits when the national systems for PAs are based on the protection of previously unprotected public lands. Given that not all PAs are established to avoid deforestation, results also admit the potential for future studies to include other outcomes including forest degradation (not just deforestation), biodiversity, wildlife, primary forests (not forests in general), among others.
The previous individual patient data meta-analyses of chemotherapy in locally advanced non-small-cell lung cancer (NSCLC) showed that adding sequential or concomitant chemotherapy to radiotherapy ...improved survival. The NSCLC Collaborative Group performed a meta-analysis of randomized trials directly comparing concomitant versus sequential radiochemotherapy.
Systematic searches for trials were undertaken, followed by central collection, checking, and reanalysis of updated individual patient data. Results from trials were combined using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival; secondary outcomes were progression-free survival, cumulative incidences of locoregional and distant progression, and acute toxicity.
Of seven eligible trials, data from six trials were received (1,205 patients, 92% of all randomly assigned patients). Median follow-up was 6 years. There was a significant benefit of concomitant radiochemotherapy on overall survival (HR, 0.84; 95% CI, 0.74 to 0.95; P = .004), with an absolute benefit of 5.7% (from 18.1% to 23.8%) at 3 years and 4.5% at 5 years. For progression-free survival, the HR was 0.90 (95% CI, 0.79 to 1.01; P = .07). Concomitant treatment decreased locoregional progression (HR, 0.77; 95% CI, 0.62 to 0.95; P = .01); its effect was not different from that of sequential treatment on distant progression (HR, 1.04; 95% CI, 0.86 to 1.25; P = .69). Concomitant radiochemotherapy increased acute esophageal toxicity (grade 3-4) from 4% to 18% with a relative risk of 4.9 (95% CI, 3.1 to 7.8; P < .001). There was no significant difference regarding acute pulmonary toxicity.
Concomitant radiochemotherapy, as compared with sequential radiochemotherapy, improved survival of patients with locally advanced NSCLC, primarily because of a better locoregional control, but at the cost of manageable increased acute esophageal toxicity.
•Conventional methods can overestimate the avoided deforestation of PAs.•We found that protection reduced deforestation in approximately 6% of the protected forests.•Conventional approaches fail to ...control for observable covariates correlated with both protection and deforestation.•This research will help decision-making in the framework of international climate change mitigation policies, such as REDD+.
For many decades, protected areas (PAs) have been considered by decision makers and conservation practitioners as one of the most common policies to promote biodiversity conservation. Diverse studies have assessed the impact of conservation policies at global and regional levels by comparing deforestation rates between PAs and unprotected areas. Most of these studies are based on conventional methods and could overestimate the avoided deforestation of PAs by omitting from their analyses the lack of randomness in the allocation of forest protection.
We demonstrate that estimates of effectiveness can be substantially improved by controlling for biases along dimensions that are observable and testing the sensitivity of estimates of potential hidden biases. We used matching methods to evaluate the impact on deforestation of Ecuador's tropical Andean forest protected-area system between 1990 and 2008. We found that protection reduced deforestation in approximately 6% of the protected forests. These would have been deforested had they not been protected. Conventional approaches to estimate conservation impact, which fail to control for observable covariates correlated with both protection and deforestation, substantially overestimate avoided deforestation. Our conclusions are robust to potential hidden bias, as well as to changes in modeling assumptions. In addition, it is assumed that this research will help decision-making in the framework of international climate change mitigation policies, such as REDD+.
The role of postoperative radiotherapy (PORT) in the treatment of patients with completely resected non-small cell lung cancer (NSCLC) was not clear. A systematic review and individual participant ...data meta-analysis was undertaken to evaluate available evidence from randomised controlled trials (RCTs). These results were first published in Lung Cancer in 2013.
To evaluate the effects of PORT on survival and recurrence in patients with completely resected NSCLC. To investigate whether predefined patient subgroups benefit more or less from PORT.
We supplemented MEDLINE and CANCERLIT searches (1965 to 8 July 2016) with information from trial registers, handsearching of relevant meeting proceedings and discussion with trialists and organisations.
We included trials of surgery versus surgery plus radiotherapy, provided they randomised participants with NSCLC using a method that precluded prior knowledge of treatment assignment.
We carried out a quantitative meta-analysis using updated information from individual participants from all randomised trials. We sought data on all participants from those responsible for the trial. We obtained updated individual participant data (IPD) on survival and date of last follow-up, as well as details on treatment allocation, date of randomisation, age, sex, histological cell type, stage, nodal status and performance status. To avoid potential bias, we requested information on all randomised participants, including those excluded from investigators' original analyses. We conducted all analyses on intention-to-treat on the endpoint of survival.
We identified 14 trials evaluating surgery versus surgery plus radiotherapy. Individual participant data were available for 11 of these trials, and our analyses are based on 2343 participants (1511 deaths). Results show a significant adverse effect of PORT on survival, with a hazard ratio of 1.18, or an 18% relative increase in risk of death. This is equivalent to an absolute detriment of 5% at two years (95% confidence interval (CI) 2% to 9%), reducing overall survival from 58% to 53%. Subgroup analyses showed no differences in effects of PORT by any participant subgroup covariate.We did not undertake analysis of the effects of PORT on quality of life and adverse events. Investigators did not routinely collect quality of life information during these trials, and it was unlikely that any benefit of PORT would offset the observed survival disadvantage. We considered risk of bias in the included trials to be low.
Results from 11 trials and 2343 participants show that PORT is detrimental to those with completely resected non-small cell lung cancer and should not be used in the routine treatment of such patients. Results of ongoing RCTs will clarify the effects of modern radiotherapy in patients with N2 tumours.
Objectives This study sought to investigate long-term cardiovascular mortality and its relationship to the use of radiotherapy for breast cancer. Background Cardiovascular diseases are among the main ...long-term complications of radiotherapy, but knowledge is limited regarding long-term risks because published studies have, on average, <20 years of follow-up. Methods A total of 4,456 women who survived at least 5 years after treatment of a breast cancer at the Institut Gustave Roussy between 1954 and 1984 were followed up for mortality until the end of 2003, for over 28 years on average. Results A total of 421 deaths due to cardiovascular diseases were observed, of which 236 were due to cardiac disease. Women who had received radiotherapy had a 1.76-fold (95% confidence interval CI: 1.34 to 2.31) higher risk of dying of cardiac disease and a 1.33-fold (95% CI: 0.99 to 1.80) higher risk of dying of vascular disease than those who had not received radiotherapy. Among women who had received radiotherapy, those who had been treated for a left-sided breast cancer had a 1.56-fold (95% CI: 1.27 to 1.90) higher risk of dying of cardiac disease than those treated for a right-sided breast cancer. This relative risk increased with time since the breast cancer diagnosis (p = 0.05). Conclusions This study confirmed that radiotherapy, as delivered until the mid-1980s, increased the long-term risk of dying of cardiovascular diseases. The long-term risk of dying of cardiac disease is a particular concern for women treated for a left-sided breast cancer with contemporary tangential breast or chest wall radiotherapy. This risk may increase with a longer follow-up, even after 20 years following radiotherapy.
Payments for environmental services (PES) are popular despite little empirical evidence of their effectiveness. We estimate the impact of PES on forest cover in a region known for exemplary ...implementation of one of the best-known and longest-lived PES programs. Our evaluation design combines sampling that incorporates prematching, data from remote sensing and household surveys, and empirical methods that include partial identification with weak assumptions, difference-in-differences matching estimators, and tests of sensitivity to unobservable heterogeneity. PES in our study site increased participating farm forest cover by about 11% to 17% of the mean area under PES contract over eight years.
PURPOSE Based on 5-year or shorter-term follow-up data in recent randomized trials, adjuvant cisplatin-based chemotherapy is now generally recommended after complete surgical resection for patients ...with non-small-cell lung cancer (NSCLC). We evaluated the results of the International Adjuvant Lung Cancer Trial study with three additional years of follow-up. PATIENTS AND METHODS Patients with completely resected NSCLC were randomly assigned to three or four cycles of cisplatin-based chemotherapy or to observation. Cox models were used to evaluate treatment effect according to follow-up duration. Results The trial included 1,867 patients with a median follow-up of 7.5 years. Results showed a beneficial effect of adjuvant chemotherapy on overall survival (hazard ratio HR, 0.91; 95% CI, 0.81 to 1.02; P = .10) and on disease-free survival (HR, 0.88; 95% CI, 0.78 to 0.98; P = .02). However, there was a significant difference between the results of overall survival before and after 5 years of follow-up (HR, 0.86; 95% CI, 0.76 to 0.97; P = .01 v HR, 1.45; 95% CI, 1.02 to 2.07; P = .04) with P = .006 for interaction. Similar results were observed for disease-free survival. The analysis of non-lung cancer deaths for the whole period showed an HR of 1.34 (95% CI, 0.99 to 1.81; P = .06). CONCLUSION These results confirm the significant efficacy of adjuvant chemotherapy at 5 years. The difference in results beyond 5 years of follow-up underscores the need for the long-term follow-up of other adjuvant lung cancer trials and for a better identification of patients deriving long-term benefit from adjuvant chemotherapy.
Summary Background The optimum dose of prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (SCLC) is unknown. A meta-analysis suggested that the incidence of brain ...metastases might be reduced with higher PCI doses. This randomised clinical trial compared the effect of standard versus higher PCI doses on the incidence of brain metastases. Methods Between September, 1999, and December, 2005, 720 patients with limited-stage SCLC in complete remission after chemotherapy and thoracic radiotherapy from 157 centres in 22 countries were randomly assigned to a standard (n=360, 25 Gy in 10 daily fractions of 2·5 Gy) or higher PCI total dose (n=360, 36 Gy) delivered using either conventional (18 daily fractions of 2 Gy) or accelerated hyperfractionated (24 fractions in 16 days with two daily sessions of 1·5 Gy separated by a minimum interval of 6 h) radiotherapy. All of the treatment schedules excluded weekends. Randomisation was stratified according to medical centre, age (≤60 and >60 years), and interval between the start of induction treatment and the date of randomisation (≤90, 91–180, and >180 days). Eligible patients were randomised blindly by the data centre of the Institut Gustave Roussy (PCI99-01 and IFCT) using minimisation, and by the data centres of EORTC (EORTC ROG and LG) and RTOG (for CALGB, ECOG, RTOG, and SWOG), both using block stratification. The primary endpoint was the incidence of brain metastases at 2 years. Analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov number NCT00005062. Findings Five patients in the standard-dose group and four in the higher-dose group did not receive PCI; nonetheless, all randomised patients were included in the effectiveness anlysis. After a median follow-up of 39 months (range 0–89 months), 145 patients had brain metastases; 82 in the standard-dose group and 63 in the higher-dose group. There was no significant difference in the 2-year incidence of brain metastases between the standard PCI dose group and the higher-dose group, at 29% (95% CI 24–35) and 23% (18–29), respectively (hazard ratio HR 0·80 95% CI 0·57–1·11, p=0·18). 226 patients in the standard-dose group and 252 in the higher-dose group died; 2-year overall survival was 42% (95% CI 37–48) in the standard-dose group and 37% (32–42) in the higher-dose group (HR 1·20 1·00–1·44; p=0·05). The lower overall survival in the higher-dose group is probably due to increased cancer-related mortality: 189 patients in the standard group versus 218 in the higher-dose group died of progressive disease. Five serious adverse events occurred in the standard-dose group versus zero in the higher-dose group. The most common acute toxic events were fatigue (106 30% patients in the standard-dose group vs 121 34% in the higher-dose group), headache (85 24% vs 99 28%), and nausea or vomiting (80 23% vs 101 28%). Interpretation No significant reduction in the total incidence of brain metastases was observed after higher-dose PCI, but there was a significant increase in mortality. PCI at 25 Gy should remain the standard of care in limited-stage SCLC. Funding Institut Gustave-Roussy, Association pour la Recherche sur le Cancer (2001), Programme Hospitalier de Recherche Clinique (2007). The European Organisation for Research and Treatment of Cancer (EORTC) contribution to this trial was supported by grants 5U10 CA11488-30 through 5U10 CA011488-38 from the US National Cancer Institute.
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