Practical robustness evaluation in radiotherapy - A photon and proton-proof alternative to PTV-based plan evaluation

Background and purpose: A planning target volume (PTV) in photon treatments aims to ensure that the clinical target volume (CTV) receives adequate dose despite treatment uncertainties. The underlying static dose cloud approximation (the assumption that the dose distribution is invariant to errors) is problematic in intensity modulated proton treatments where range errors should be taken into account as well. The purpose of this work is to introduce a robustness evaluation method that is applicable to photon and proton treatments and is consistent with (historic) PTV-based treatment plan evaluations. Materials and methods: The limitation of the static dose cloud approximation was solved in a multi-scenario simulation by explicitly calculating doses for various treatment scenarios that describe possible errors in the treatment course. Setup errors were the same as the CTV-PTV margin and the underlying theory of 3D probability density distributions was extended to 4D to include range errors, maintaining a 90% confidence level. Scenario dose distributions were reduced to voxel-wise minimum and maximum dose distributions; the first to evaluate CTV coverage and the second for hot spots. Acceptance criteria for CTV D98 and D2 were calibrated against PTV-based criteria from historic photon treatment plans. Results: CTV D98 in worst case scenario dose and voxel-wise minimum dose showed a very strong correlation with scenario average D98 (R-2 > 0.99). The voxel-wise minimum dose visualised CTV dose conformity and coverage in 3D in agreement with PTV-based evaluation in photon therapy. Criteria for CTV D98 and D2 of the voxel-wise minimum and maximum dose showed very strong correlations to PTV D98 and D2 (R-2 > 0.99) and on average needed corrections of -0.9% and +2.3%, respectively. Conclusions: A practical approach to robustness evaluation was provided and clinically implemented for PTV-less photon and proton treatment planning, consistent with PTV evaluations but without its static dose cloud approximation. (C) 2019 The Authors. Published by Elsevier B.V

Compositional characteristics and spatial distribution of enriched Icelandic mantle components

Author Posting. © The Authors, 2010. This is the author's version of the work. It is posted here by permission of Oxford University Press for personal use, not for redistribution. The definitive version was published in Journal of Petrology 51 (2010): 1447-1475, doi:10.1093/petrology/egq025.We present compositional data on a suite of 18 primitive neovolcanic alkali basalts from three flank zone regions in Iceland (Vestmannaeyjar in the south, Snæfell in the east, and Snæfellsnes in the west) that are peripheral to the main rift zones that are dominated by tholeiitic basalts. This study integrates He isotope data with radiogenic isotope data (Sr-Nd-Pb-Hf), stable isotope data (δ18O), and trace element data to characterise the compositional features of the trace-elementenriched components of the Icelandic mantle. We also present high-precision Pb isotope data on an additional 57 lava samples from the flank zones (including Öræfajökull in the south-east) and the Northern and Eastern rift zones. Most Icelandic lavas have negative Δ207Pb (–4 to –1), with higher values (–1 to +4) found only in samples from Öræfajökull, Snæfell, and parts of the Reykjanes Peninsula. At Snæfell, this EM1-type component is characterised by a low δ18Oolivine signature (+4.1‰ to +4.6‰), moderate 206Pb/204Pb values (18.4-18.6) and MORB-like 3He/4He (6.9-7.5 R/RA). Samples from Vestmannaeyjar and Snæfellsnes have mantle-like δ18Oolivine (+4.9‰ to +5.0‰), and radiogenic 206Pb/204Pb values (18.9-19.3) that fall on the NHRL for 208Pb/204Pb (Δ208Pb –5 to +5). Compared to the Vestmannaeyjar lavas, Snæfellsnes lavas have higher La/YbN (5-11 vs. 3-5), lower εNd (5.5-6.5 vs. 6.8-7.6) and lower 3He/4He (6.3-8.6 R/RA vs. 11.4-13.5 R/RA). Therefore, the most trace element enriched components in the Icelandic mantle are not the carriers of the high 3He/4He values (> 15 R/RA) found in some lavas on Iceland and the adjacent ridges, and instead are consistent with degassed, recycled components. Even after excluding the EM1-type high Δ207Pb samples, high-precision Pb isotope data produce a kinked array on an 206Pb/204Pb vs. 208Pb/204Pb plot, which is not consistent with simple binary mixing between two end-members. This requires significant lateral heterogeneity within the Icelandic mantle and the presence of more than just two compositionally-distinct local mixing end-member components. Samples from each of the main axial rift zones define different trends. Despite the tectonic continuity between the Northern Volcanic Zone and the Eastern Volcanic Zone, lavas from these two rift zones define separate sub-parallel linear arrays. Lavas from the adjacent Western Volcanic Zone and the Eastern Volcanic Zone define oblique linear arrays that converge on a common local end-member that is not involved in the magmatism of the Northern Volcanic Zone. Therefore, there is a distinct NE-SW compositional heterogeneity within the Icelandic mantle.work was funded primarily by the Danish National Research Foundation through a grant to the former Danish Lithosphere Centre, with additional funding from the University of Iowa for the oxygen isotope analyses

Individualized early death and long-term survival prediction after stereotactic radiosurgery for brain metastases of non-small cell lung cancer:Two externally validated nomograms

Introduction Commonly used clinical models for survival prediction after stereotactic radiosurgery (SRS) for brain metastases (BMs) are limited by the lack of individual risk scores and disproportionate prognostic groups. In this study, two nomograms were developed to overcome these limitations. Methods 495 patients with BMs of NSCLC treated with SRS for a limited number of BMs in four Dutch radiation oncology centers were identified and divided in a training cohort (n = 214, patients treated in one hospital) and an external validation cohort n = 281, patients treated in three other hospitals). Using the training cohort, nomograms were developed for prediction of early death (<3 months) and long-term survival (>12 months) with prognostic factors for survival. Accuracy of prediction was defined as the area under the curve (AUC) by receiver operating characteristics analysis for prediction of early death and long term survival. The accuracy of the nomograms was also tested in the external validation cohort. Results Prognostic factors for survival were: WHO performance status, presence of extracranial metastases, age, GTV largest BM, and gender. Number of brain metastases and primary tumor control were not prognostic factors for survival. In the external validation cohort, the nomogram predicted early death statistically significantly better (p < 0.05) than the unfavorable groups of the RPA, DS-GPA, GGS, SIR, and Rades 2015 (AUC = 0.70 versus range AUCs = 0.51–0.60 respectively). With an AUC of 0.67, the other nomogram predicted 1 year survival statistically significantly better (p < 0.05) than the favorable groups of four models (range AUCs = 0.57–0.61), except for the SIR (AUC = 0.64, p = 0.34). The models are available on www.predictcancer.org. Conclusion The nomograms predicted early death and long-term survival more accurately than commonly used prognostic scores after SRS for a limited number of BMs of NSCLC. Moreover these nomograms enable individualized probability assessment and are easy into use in routine clinical practice

Differences in the association of time to treatment initiation and survival according to various head and neck cancer sites in a nationwide cohort

Objectives: To assess whether there are differences in the effects of time to treatment interval (TTI) on patient survival for head and neck cancer (HNC) sites in order to provide evidence that can support decision-making regarding prioritizing treatment. Materials and methods: Patients in the Netherlands with a first primary HNC without distant metastasis between 2010 and 2014 were included for analysis (N = 10,486). TTI was defined as the time from pathologic diagnosis to the start of initial treatment. Overall survival (OS), cox regression analyses and cubic spline hazard models were calculated and visualized. Results: Overall, the hazard of dying was higher (HR = 1.003; 95 % CI 1.001–1.005) with each additional day until treatment initiation. The pattern, as visualized in cubic spline graphs, differed by site the hazard increased more steeply with increasing TTI for oral cavity cancer. For oropharyngeal and laryngeal cancer, a slight increase commenced after a longer TTI than for oral cavity cancer, while there was hardly an increase in hazard with increasing TTI for hypopharyngeal cancer. Conclusion: The relationship between longer TTI and decreased survival was confirmed, but slight variations in the pattern of the hazard of dying by TTI by tumour site were observed. These findings could support decisions on prioritizing treatment. However, other aspects such as extent of treatment and quality of life should be investigated further so this can also be included

How and when plume zonation appeared during the 132 Myr evolution of the Tristan Hotspot

Increasingly, spatial geochemical zonation, present as geographically distinct, subparallel trends, is observed along hotspot tracks, such as Hawaii and the Galapagos. The origin of this zonation is currently unclear. Recently zonation was found along the last B70 Myr of the Tristan-Gough hotspot track. Here we present new Sr–Nd–Pb–Hf isotope data from the older parts of this hotspot track (Walvis Ridge and Rio Grande Rise) and re-evaluate published data from the Etendeka and Parana flood basalts erupted at the initiation of the hotspot track. We show that only the enriched Gough, but not the less-enriched Tristan, component is present in the earlier (70–132 Ma) history of the hotspot. Here we present a model that can explain the temporal evolution and origin of plume zonation for both the Tristan-Gough and Hawaiian hotspots, two end member types of zoned plumes, through processes taking place in the plume sources at the base of the lower mantle

Late Cretaceous tectonic history of the Sierra‐Salinia‐Mojave arc as recorded in conglomerates of the Upper Cretaceous and Paleocene Gualala Formation, northern California

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95005/1/jgrb14012.pd

Primary carbonatite melt from deeply subducted oceanic crust

Partial melting in the Earth's mantle plays an important part in generating the geochemical and isotopic diversity observed in volcanic rocks at the surface. Identifying the composition of these primary melts in the mantle is crucial for establishing links between mantle geochemical 'reservoirs' and fundamental geodynamic processes. Mineral inclusions in natural diamonds have provided a unique window into such deep mantle processes. Here we provide experimental and geochemical evidence that silicate mineral inclusions in diamonds from Juina, Brazil, crystallized from primary and evolved carbonatite melts in the mantle transition zone and deep upper mantle. The incompatible trace element abundances calculated for a melt coexisting with a calcium-titanium-silicate perovskite inclusion indicate deep melting of carbonated oceanic crust, probably at transition-zone depths. Further to perovskite, calcic-majorite garnet inclusions record crystallization in the deep upper mantle from an evolved melt that closely resembles estimates of primitive carbonatite on the basis of volcanic rocks. Small-degree melts of subducted crust can be viewed as agents of chemical mass-transfer in the upper mantle and transition zone, leaving a chemical imprint of ocean crust that can possibly endure for billions of years.4 page(s

LINAC based stereotactic radiosurgery for multiple brain metastases: guidance for clinical implementation

Introduction: Stereotactic radiosurgery (SRS) is a promising treatment option for patients with multiple brain metastases (BM). Recent technical advances have made LINAC based SRS a patient friendly technique, allowing for accurate patient positioning and a short treatment time. Since SRS is increasingly being used for patients with multiple BM, it remains essential that SRS be performed with the highest achievable quality in order to prevent unnecessary complications such as radionecrosis. The purpo

Potential controls of isoprene in the surface ocean

Isoprene surface ocean concentrations and vertical distribution, atmospheric mixing ratios, and calculated sea-to-air fluxes spanning approximately 125° of latitude (80°N–45°S) over the Arctic and Atlantic Oceans are reported. Oceanic isoprene concentrations were associated with a number of concurrently monitored biological variables including chlorophyll a (Chl a), photoprotective pigments, integrated primary production (intPP), and cyanobacterial cell counts, with higher isoprene concentrations relative to all respective variables found at sea surface temperatures greater than 20°C. The correlation between isoprene and the sum of photoprotective carotenoids, which is reported here for the first time, was the most consistent across all cruises. Parameterizations based on linear regression analyses of these relationships perform well for Arctic and Atlantic data, producing a better fit to observations than an existing Chl a-based parameterization. Global extrapolation of isoprene surface water concentrations using satellite-derived Chl a and intPP reproduced general trends in the in situ data and absolute values within a factor of 2 between 60% and 85%, depending on the data set and algorithm used