Effects of anatomical changes on pencil beam scanning proton plans in locally advanced NSCLC patients

Daily anatomical variations can cause considerable differences between delivered and planned dose. This study simulates and evaluates these effects in spot-scanning proton therapy for lung cancer patients. Robust intensity modulated treatment plans were designed on the mid-position CT scan for sixteen locally advanced lung cancer patients. To estimate dosimetric uncertainty, deformable registration was performed on their daily CBCTs to generate 4DCT equivalent scans for each fraction and to map recomputed dose to a common frame. Without adaptive planning, eight patients had an undercoverage of the targets of more than 2GyE (maximum of 14.1GyE) on the recalculated treatment dose from the daily anatomy variations including respiration. In organs at risk, a maximum increase of 4.7GyE in the D1 was found in the mediastinal structures. The effect of respiratory motion alone is smaller: 1.4GyE undercoverage for targets and less than 1GyE for organs at risk. Daily anatomical variations over the course of treatment can cause considerable dose differences in the robust planned dose distribution. An advanced planning strategy including knowledge of anatomical uncertainties would be recommended to improve plan robustness against interfractional variations. For large anatomical changes, adaptive therapy is mandator

Myocardial dysfunction in long-term breast cancer survivors treated at ages 40-50years

AimsAnthracyclines increase heart failure (HF) risk, but the long-term prevalence of myocardial dysfunction in young breast cancer (BC) survivors is unknown. Early measures of left ventricular myocardial dysfunction are needed to identify BC patients at risk of symptomatic HF. Methods and resultsWithin an established cohort, we studied markers for myocardial dysfunction among 569 women, who were 5-7years (n = 277) or 10-12years (n = 292) after BC treatment at ages 40-50years. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were assessed by echocardiography. N-terminal pro-brain natriuretic peptide (NT-proBNP) was measured in serum. Associations between patient-related and treatment-related risk factors and myocardial dysfunction were evaluated using linear and logistic regression. Median ages at BC diagnosis and cardiac assessment were 46.7 and 55.5years, respectively. Anthracycline-treated patients (n = 313), compared to the no-anthracycline group (n = 256), more often had decreased LVEF (10% vs. 4%), impaired GLS (34% vs. 27%) and elevated NT-proBNP (23% vs. 8%). GLS and LVEF declined in a linear fashion with increasing cumulative anthracycline dose (GLS: +0.23 and LVEF: -0.40 per cycle of 60mg/m(2); P125ng/L was highest for patients who received 241-300mg/m(2) anthracycline dose compared to the no-anthracycline group (odds ratio: 3.30, 95% confidence interval: 1.83-5.96). ConclusionImpaired GLS and increased NT-proBNP levels are present in a substantial proportion of young BC survivors treated with anthracyclines. Whether this will lead to future cardiac disease needs to be evaluated by longitudinal assessment

Mercury in the Black Sea:New Insights From Measurements and Numerical Modeling

Redox conditions and organic matter control marine methylmercury (MeHg) production. The Black Sea is the world's largest and deepest anoxic basin and is thus ideal to study Hg species along the extended redox gradient. Here we present new dissolved Hg and MeHg data from the 2013 GEOTRACES MEDBlack cruise (GN04_leg2) that we integrated into a numerical 1-D model, to track the fate and dynamics of Hg and MeHg. Contrary to a previous study, our new data show highest MeHg concentrations in the permanently anoxic waters. Observed MeHg/Hg percentage (range 9-57%) in the anoxic waters is comparable to other subsurface maxima in oxic open-ocean waters. With the modeling we tested for various Hg methylation and demethylation scenarios along the redox gradient. The results show that Hg methylation must occur in the anoxic waters. The model was then used to simulate the time evolution (1850-2050) of Hg species in the Black Sea. Our findings quantify (1) inputs and outputs of Hg-T (similar to 31 and similar to 28 kmol yr(-1)) and MeHgT (similar to 5 and similar to 4 kmol yr(-1)) to the basin, (2) the extent of net demethylation occurring in oxic (similar to 1 kmol yr(-1)) and suboxic water (similar to 6 kmol yr(-1)), (3) and the net Hg methylation in the anoxic waters of the Black Sea (similar to 11 kmol yr(-1)). The model was also used to estimate the amount of anthropogenic Hg (85-93%) in the Black Sea

Case study on the efficacy of a lanthanum-enriched clay (Phoslock®) in controlling eutrophication in Lake Het Groene Eiland (The Netherlands)

Lake Het Groene Eiland was created in the beginning of 2008 by construction of dikes for isolating it from the surrounding 220-ha water body. This so-called claustrum of 5 ha was treated using lanthanum-modified clay (Phoslock®) to control eutrophication and mitigate cyanobacterial nuisance. Cyanobacteria chlorophyll-a were significantly lower in the claustrum than those in the reference water body, where a massive bloom developed in summer, 2008. However, PO4-P and TP did not statistically differ in these two waters. TN and NO3-N were significantly lower in the claustrum, where dense submerged macrophytes beds developed. Lanthanum concentrations were elevated after the applications of the modified clay in the claustrum, but filterable lanthanum dropped rapidly below the Dutch standard of 10.1 μg l−1. During winter, dozens of Canada geese resided at the claustrum. Geese droppings contained an average of 2 mg PO4-P g−1 dry weight and 12 mg NH3-N g−1 dry weight and might present a growing source of nutrients to the water. Constructing the claustrum enabled unrestricted bathing in subsequent three summers, as no swimming bans had to be issued due to cyanobacteria blooms. However, the role of the modified clay in this positive outcome remains unclear, and longevity of the measures questionable.

Closing a gap in tropical forest biomass estimation : taking crown mass variation into account in pantropical allometries

Accurately monitoring tropical forest carbon stocks is a challenge that remains outstanding. Allometric models that consider tree diameter, height and wood density as predictors are currently used in most tropical forest carbon studies. In particular, a pantropical biomass model has been widely used for approximately a decade, and its most recent version will certainly constitute a reference model in the coming years. However, this reference model shows a systematic bias towards the largest trees. Because large trees are key drivers of forest carbon stocks and dynamics, understanding the origin and the consequences of this bias is of utmost concern. In this study, we compiled a unique tree mass data set of 673 trees destructively sampled in five tropical countries (101 trees > 100 cm in diameter) and an original data set of 130 forest plots (1 ha) from central Africa to quantify the prediction error of biomass allometric models at the individual and plot levels when explicitly taking crown mass variations into account or not doing so. We first showed that the proportion of crown to total tree aboveground biomass is highly variable among trees, ranging from 3 to 88 %. This proportion was constant on average for trees = 45 Mg. This increase coincided with a progressive deviation between the pantropical biomass model estimations and actual tree mass. Taking a crown mass proxy into account in a newly developed model consistently removed the bias observed for large trees (> 1 Mg) and reduced the range of plot- level error (in %) from [-23; 16] to [0; 10]. The disproportionally higher allocation of large trees to crown mass may thus explain the bias observed recently in the reference pantropical model. This bias leads to far- from- negligible, but often overlooked, systematic errors at the plot level and may be easily corrected by taking a crown mass proxy for the largest trees in a stand into account, thus suggesting that the accuracy of forest carbon estimates can be significantly improved at a minimal cost

Evidence of free tropospheric and long-range transport of microplastic at Pic du Midi Observatory

The emerging threat of atmospheric microplastic pollution has prompted researchers to study areas previously considered beyond the reach of plastic. Investigating the range of atmospheric microplastic transport is key to understanding the global extent of this problem. While atmospheric microplastics have been discovered in the planetary boundary layer, their occurrence in the free troposphere is relatively unexplored. Confronting this is important because their presence in the free troposphere would facilitate transport over greater distances and thus the potential to reach more distal and remote parts of the planet. Here we show evidence of 0.09–0.66 microplastics particles/m3 over 4 summer months from the Pic du Midi Observatory at 2877 meters above sea level. These results exhibit true free tropospheric transport of microplastic, and high altitude microplastic particles <50 µm (aerodynamic diameter). Analysis of air/particle history modelling shows intercontinental and trans-oceanic transport of microplastics illustrating the potential for global aerosol microplastic transport

The effect of trastuzumab on cardiac function in patients with HER2-positive metastatic breast cancer and reduced baseline left ventricular ejection fraction

We investigated the effect of trastuzumab on cardiac function in a real‐world historic cohort of patients with HER2‐positive metastatic breast cancer (MBC) with reduced baseline left ventricular ejection fraction (LVEF). Thirty‐seven patients with HER2‐positive MBC and baseline LVEF of 40% to 49% were included. Median LVEF was 46% (interquartile range [IQR] 44%‐48%) and median follow‐up was 18 months (IQR 9‐34 months). During this period, the LVEF did not worsen in 24/37 (65%) patients, while 13/37 (35%) patients developed severe cardiotoxicity defined as LVEF 5%‐points below baseline) in 3/13 (23%) patients and irreversible (defined as absolute LVEF increase 5%‐points below baseline) in 3/13 (23%) patients. Likelihood of reversibility was numerically higher in patients who received cardio‐protective medications (CPM), including ACE‐inhibitors, beta‐blockers and angiotensine‐2 inhibitors, compared to those who did not receive any CPM (71% vs 13%, P = .091). Sixty‐five percent of patients who received trastuzumab for HER2‐positive MBC did not develop severe cardiotoxicity during a median follow‐up of 18 months, despite having a compromised baseline LVEF. If severe cardiotoxicity occurred, it was at least partly reversible in more than two‐thirds of the cases. Risks and benefits of trastuzumab use should be balanced carefully in this vulnerable population

Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial.

PURPOSE: In SOLO1/GOG 3004 (ClinicalTrials.gov identifier: NCT01844986), maintenance therapy with the poly(ADP-ribose) polymerase inhibitor olaparib provided a sustained progression-free survival benefit in patients with newly diagnosed advanced ovarian cancer and a BRCA1 and/or BRCA2 (BRCA) mutation. We report overall survival (OS) after a 7-year follow-up, a clinically relevant time point and the longest follow-up for any poly(ADP-ribose) polymerase inhibitor in the first-line setting. METHODS: This double-blind phase III trial randomly assigned patients with newly diagnosed advanced ovarian cancer and a BRCA mutation in clinical response to platinum-based chemotherapy to maintenance olaparib (n = 260) or placebo (n = 131) for up to 2 years. A prespecified descriptive analysis of OS, a secondary end point, was conducted after a 7-year follow-up. RESULTS: The median duration of treatment was 24.6 months with olaparib and 13.9 months with placebo, and the median follow-up was 88.9 and 87.4 months, respectively. The hazard ratio for OS was 0.55 (95% CI, 0.40 to 0.76; P = .0004 [P < .0001 required to declare statistical significance]). At 7 years, 67.0% of olaparib patients versus 46.5% of placebo patients were alive, and 45.3% versus 20.6%, respectively, were alive and had not received a first subsequent treatment (Kaplan-Meier estimates). The incidence of myelodysplastic syndrome and acute myeloid leukemia remained low, and new primary malignancies remained balanced between treatment groups. CONCLUSION: Results indicate a clinically meaningful, albeit not statistically significant according to prespecified criteria, improvement in OS with maintenance olaparib in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation and support the use of maintenance olaparib to achieve long-term remission in this setting; the potential for cure may also be enhanced. No new safety signals were observed during long-term follow-up