Neutrophil/lymphocyte ratio (NLR), defined as absolute neutrophils count divided by absolute lymphocytes count, has been reported as poor prognostic factor in several neoplastic diseases but only a ...few data are available about unresectable metastatic colorectal cancer (mCRC) patients (pts). The aim of our study was to evaluate the prognostic and predictive role of NLR in the TRIBE trial.
Pts enrolled in TRIBE trial were included. TRIBE is a multicentre phase III trial randomizing unresectable and previously untreated mCRC pts to receive FOLFOXIRI or FOLFIRI plus bevacizumab. A cut-off value of 3 was adopted to discriminate pts with low (NLR<3) versus high (NLR≥3) NLR, as primary analysis. As secondary analysis, NLR was treated as an ordinal variable with three levels based on terciles distribution.
NLR at baseline was available for 413 patients. After multiple imputation at univariate analysis, patients with high NLR had significantly shorter progression-free survival (PFS) hazard ratio (HR) 1.27 (95% CI 1.05–1.55), P=0.017 and overall survival (OS) HR 1.56 (95% CI 1.25–1.95), P<0.001 than patients with low NLR. In the multivariable model, NLR retained a significant association with OS HR 1.44 (95% CI 1.14–1.82), P=0.014 but not with PFS HR 1.18 (95% CI 0.95–1.46), P=0.375. No interaction effect between treatment arm and NLR was evident in terms of PFS (P for interaction=0.536) or OS (P for interaction=0.831). Patients with low HR 0.84 (95% CI 0.64–1.08) and high HR 0.73 (95% CI 0.54–0.97) NLR achieved similar PFS benefit from the triplet and consistent results were obtained in terms of OS HR 0.83 (95% CI 0.62–1.12) for low NLR; HR 0.82 (95% CI 0.59–1.12) for high NLR.
This study confirmed the prognostic role of NLR in mCRC pts treated with bevacizumab plus chemotherapy in the first line, showing the worse prognosis of pts with high NLR. The advantage of the triplet is independent of NLR at baseline.
Despite major advances in the management of metastatic colorectal cancer (mCRC) with liver-only involvement, relapse rates are high and reliable prognostic markers are needed.
To assess the ...prognostic impact of BRAF and RAS mutations in a large series of liver-resected patients, medical records of 3024 mCRC patients were reviewed. Eligible cases undergoing potentially curative liver resection were selected. BRAF and RAS mutational status was tested on primary and/or metastases by means of pyrosequencing and mass spectrometry genotyping assay. Primary endpoint was relapse-free survival (RFS).
In the final study population (N=309) BRAF mutant, RAS mutant and all wild-type (wt) patients were 12(4%), 160(52%) and 137(44%), respectively. Median RFS was 5.7, 11.0 and 14.4 months respectively and differed significantly (Log-rank, P=0.043). At multivariate analyses, BRAF mutant had a higher risk of relapse in comparison to all wt (multivariate hazard ratio (HR)=2.31; 95% CI, 1.09-4.87; P=0.029) and to RAS mutant (multivariate HR=2.06; 95% CI, 1.02-4.14; P=0.044). Similar results were obtained in terms of overall survival. Compared with all wt patients, RAS mutant showed a higher risk of death (HR=1.47; 95% CI, 1.05-2.07; P=0.025), but such effect was lost at multivariate analyses.
BRAF mutation is associated with an extremely poor median RFS after liver resection and with higher probability of relapse and death. Knowledge of BRAF mutational status may optimise clinical decision making in mCRC patients potentially candidate to hepatic surgery. RAS status as useful marker in this setting might require further studies.
Invasive plant species pose a direct threat to biodiversity and ecosystem services. Among these, Rosa rugosa has had a severe impact on Baltic coastal ecosystems in recent decades. Accurate mapping ...and monitoring tools are essential to quantify the location and spatial extent of invasive plant species to support eradication programs. In this paper we combined RGB images obtained using an Unoccupied Aerial Vehicle, with multispectral PlanetScope images to map the extent of R. rugosa at seven locations along the Estonian coastline. We used RGB-based vegetation indices and 3D canopy metrics in combination with a random forest algorithm to map R. rugosa thickets, obtaining high mapping accuracies (Sensitivity = 0.92, specificity = 0.96). We then used the R. rugosa presence/absence maps as a training dataset to predict the fractional cover based on multispectral vegetation indices derived from the PlanetScope constellation and an Extreme Gradient Boosting algorithm (XGBoost). The XGBoost algorithm yielded high fractional cover prediction accuracies (RMSE = 0.11, R2 = 0.70). An in-depth accuracy assessment based on site-specific validations revealed notable differences in accuracy between study sites (highest R2 = 0.74, lowest R2 = 0.03). We attribute these differences to the various stages of R. rugosa invasion and the density of thickets. In conclusion, the combination of RGB UAV images and multispectral PlanetScope images is a cost-effective method to map R. rugosa in highly heterogeneous coastal ecosystems. We propose this approach as a valuable tool to extend the highly local geographical scope of UAV assessments into wider areas and regional evaluations.
•UAV rgb data enables accurate monitoring of Rosa rugosa in coastal areas.•Photogrammetric canopy metrics play a key role in the detection of Rosa rugosa.•UAV and PlanetScope data fusion accurately predicts Rosa rugosa over large areas.
Abstract Background BRAF V600E mutation plays a negative prognostic role in metastatic colorectal cancer (mCRC), leading to a median Progression Free Survival (PFS) of 4–6 months with first-line ...conventional treatments. Our group recently reported in a retrospective exploratory analysis of a phase II trial that FOLFOXIRI (5-FU/LV+Oxaliplatin+Irinotecan) plus bevacizumab might allow to achieve remarkable results in terms of PFS and Overall Survival (OS) also in this poor-prognosis subgroup. The aim of this work was to prospectively validate our retrospective finding. Patients and methods This phase II trial was designed to detect an increase in 6 month-Progression Free Rate (6 m-PFR) from 45% to 80% in a population of BRAF mutant mCRC patients treated with first-line FOLFOXIRI plus bevacizumab. Secondary end-points were PFS, OS, response rate (RR) and the analysis of outcome parameters in the pooled population consisting of both retrospectively and prospectively included patients. This trial is registered with ClinicalTrials.gov, number NCT01437618. Results Two-hundred-fourteen potentially eligible mCRC patients were screened for BRAF mutational status. Fifteen BRAF mutant patients (7%) were included in the validation cohort. At a median follow up of 25.7 months, 6 m-PFR was 73%. Median PFS and OS were 9.2 and 24.1 months, respectively. In the pooled population, at a median follow up of 40.4 months, 6 m-PFR was 84%. Median PFS and OS were 11.8 and 24.1 months, respectively. Overall RR and disease control rate were 72% and 88%, respectively. Conclusion Lacking randomised trials in this specific molecular subgroup, FOLFOXIRI plus bevacizumab might be a reasonable option for the first-line treatment of BRAF mutant mCRC patients.
Seagrasses are marine flowering plants, which form extensive meadows in intertidal and shallow water marine environments. They provide a wide range of ecosystem services, which directly or indirectly ...benefit humans and can be grouped into four broad categories: provisioning (e.g. food production); regulating (e.g. carbon sequestration); supporting (e.g. primary production); and cultural (e.g. recreational, and eco-tourism). This study provides a review of publications focusing on seagrass ecosystem services provision to identify knowledge gaps and improve our understanding of the use of these habitats as nature-based solutions to societal challenges, such as climate change. Results showed that some ecosystem services, namely food provision, carbon sequestration, and maintenance of biodiversity/nursery habitats receive a higher level of focus and attention than others, such as regulation of diseases and social relations, which are rarely, if ever, included in studies. It is clear that in order to fully comprehend the nature-based solution potential held by seagrass ecosystems, studies need to consider ecosystem services as a whole, and also combine and share results across global regions, to better understand the potential impacts of degradation and loss of these ecosystems worldwide. Suggestions include applying novel technologies such as remote sensing and ecological niche modelling to address some of the main gaps in seagrass research, like meadow extent and connectivity within landscapes, to better incorporate preservation of seagrass ecosystems in marine management plans.
Coastal wetlands provide a range of important ecosystem services, yet they are under threat from a range of stressors including climate change. This is predominantly as a result of alterations to the ...hydroregime and associated edaphic factors. We used a three-year mesocosm experiment to assess changes in coastal plant community composition for three plant communities in response to altered water level and salinity scenarios. Species richness and abundance were calculated by year and abundance was plotted using rank abundance curves. The permutational multivariate analysis of variance with Bray-Curtis dissimilarity was used to examine differences among treatments in plant community composition. A Non-metric Multi-dimensional Scaling analysis (NMDS) was used to visualize the responses of communities to treatments by year. Results showed that all three plant communities responded differently to altered water levels and salinity. Species richness and abundance increased significantly in an Open Pioneer plant community while Lower and Upper Shore plant communities showed less change. Species abundances changed in all plant communities with shifts in species composition significantly influenced by temporal effects and treatment. The observed responses to experimentally altered conditions highlight the need for conservation of these important ecosystems in the face of predicted climate change, since these habitats are important for wading birds and livestock grazing.
Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, ...we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status.
Patients were randomized to receive upfront 5-fluoruracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or 5-fluoruracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab. Tumors were defined as right- or left-sided if they originated from the caecum to the transverse colon or within the splenic flexure and beyond, respectively. Patients with available information about both primary sidedness and RAS and BRAF status were included in the present analysis. Progression-free survival (PFS), overall survival (OS) and RECIST response rate were assessed according to tumor location and RAS and BRAF mutational status.
Information about primary sidedness and RAS and BRAF status was available for 358 (70.5%) out of 508 randomized patients. Patients with right-sided tumors (N=173) presented shorter OS 23.7 versus 31.0months, HR=1.42 (95% CI 1.09–1.84), P=0.010 and a trend toward shorter PFS 10.2 versus 11.5months, HR=1.24 (95% CI: 0.98–1.56), P=0.083 than those with left-sided tumors (N=185), but these associations were no longer evident when adjusting for RAS and BRAF status. Patients with right-sided tumors achieved more relative benefit from the intensification of the chemotherapy backbone in terms of both PFS (HR=0.59 versus 0.89, P for interaction=0.099) and OS (HR=0.56 versus 0.99, P for interaction=0.030) and this advantage was independent of their RAS and BRAF status.
FOLFOXIRI plus bevacizumab may be regarded as a preferred first-line treatment option for clinically selected patients with right-sided metastatic colorectal cancer irrespective of their RAS and BRAF mutational status. Trial registration: clinicaltrials.gov identifier NCT00719797.
High-resolution images obtained by multispectral cameras mounted on Unmanned Aerial Vehicles (UAVs) are helping to capture the heterogeneity of the environment in images that can be discretized in ...categories during a classification process. Currently, there is an increasing use of supervised machine learning (ML) classifiers to retrieve accurate results using scarce datasets with samples with non-linear relationships. We compared the accuracies of two ML classifiers using a pixel and object analysis approach in six coastal wetland sites. The results show that the Random Forest (RF) performs better than K-Nearest Neighbors (KNN) algorithm in the classification of pixels and objects and the classification based on pixel analysis is slightly better than the object-based analysis. The agreement between the classifications of objects and pixels is higher in Random Forest. This is likely due to the heterogeneity of the study areas, where pixel-based classifications are most appropriate. In addition, from an ecological perspective, as these wetlands are heterogeneous, the pixel-based classification reflects a more realistic interpretation of plant community distribution.
The phase III TRIBE and TRIBE2 studies randomized metastatic colorectal cancer patients to first-line FOLFOXIRI/bevacizumab or a doublet (FOLFIRI or FOLFOX)/bevacizumab. The studies demonstrated a ...significant benefit from the triplet at the price of an increased incidence of chemotherapy-related adverse events (AEs). In both trials, males and females aged between 18 and 70 years with ECOG PS ≤2 and between 71 and 75 years with ECOG PS=0 were eligible. We investigated the effect of FOLFOXIRI/bevacizumab versus doublets/bevacizumab according to age and gender.
Subgroup analyses according to age (<70 versus 70–75years) and gender were carried out for overall response rate (ORR), progression-free survival (PFS), and AE rates.
Of 1187 patients, 1005 (85%) were aged <70years and 182 (15%) 70–75years; 693 (58%) were males and 494 (42%) females. There was no evidence of interaction between age or gender and the benefit provided by the intensification of the upfront chemotherapy in terms of ORR and PFS, or the increased risk of experiencing G3/4 AEs. Elderly patients and females experienced higher rates of overall G3/4 AEs (73% versus 60%, P<0.01 and 69% versus 57%, P<0.01, respectively). Notably, in the FOLFOXIRI/bevacizumab subgroup, G3/4 diarrhea and febrile neutropenia occurred in 27% and 16% of elderly patients, respectively, while females reported high incidences of any grade nausea (67%) and vomiting (50%).
The improvements in terms of ORR and PFS of FOLFOXIRI/bevacizumab versus doublets/bevacizumab are independent of gender and age, with a similar relative increase in AEs among elderly patients and females. Initial dose reductions and possibly primary G-CSF prophylaxis should be recommended for patients between 70 and 75years old treated with FOLFOXIRI/bevacizumab, and a careful management of antiemetic prophylaxis should be considered among females.
Coastal wetlands provide a range of ecosystem services, yet they are currently under threat from global change impacts. Thus, their monitoring and assessment is vital for evaluating their status, ...extent and distribution. Remote sensing provides an excellent tool for evaluating coastal ecosystems, whether with small-scale studies using drones or national-/regional-/global-scale studies using satellite-derived data. This study used a fine-scale plant community classification of coastal meadows in Estonia derived from a multispectral camera on board unoccupied aerial vehicles (UAVs) to calculate the plant fractional cover (PFC) in Sentinel-2 MultiSpectral Instrument (MSI) sensor grids. A random forest (RF) algorithm was trained and tested with vegetation indices (VIs) calculated from the spectral bands extracted from the MSI sensor to predict the PFC. Additional RF models were trained and tested after adding a digital elevation model (DEM). After comparing the models, results show that using DEM with VIs can increase the prediction accuracy of PFC up to 2 times (R2 58 %–70 %). This suggests the use of ancillary data such as DEM to improve the prediction of empirical machine learning models, providing an appropriate approach to upscale local studies to wider areas for management and conservation purposes.
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