Acute and intermediate toxicity of 3-week radiotherapy with simultaneous integrated boost using TomoDirect: prospective series of 287 early breast cancer patients

Aims To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy® with Direct modality. Methods Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05 Gy) and SIB to the TB (48 Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6 months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria. Results The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6 months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6 months. At univariate analysis, age < 40 years, breast volume > 1000 cm3 and Dmax ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13–3.63) and 1.84 (1.26–2.67), respectively. At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good–excellent result for 86% of patients (AU)

Acute and intermediate toxicity of 3-week radiotherapy with simultaneous integrated boost using TomoDirect: prospective series of 287 early breast cancer patients.

AIMS: To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy® with Direct modality. METHODS: Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05 Gy) and SIB to the TB (48 Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6 months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria. RESULTS: The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6 months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6 months. At univariate analysis, age < 40 years, breast volume > 1000 cm3 and Dmax ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13-3.63) and 1.84 (1.26-2.67), respectively. At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good-excellent result for 86% of patients. CONCLUSIONS: Hypofractionated WB IMRT with a SIB to the TB, delivered with TomoDirect modality, is safe and well-tolerated. Most patients reported no toxicity after 6 months and good-excellent cosmesis. Predictive factors of clinically relevant toxicity might be considered during treatment planning in order to further reduce side effects.

Investigating the Size and Microstrain Influence in the Magnetic Order/Disorder State of GdCu2 Nanoparticles.

A series of GdCu 2 nanoparticles with controlled sizes ranging from 7 nm to 40 nm has been produced via high-energy inert-gas ball milling. Rietveld refinements on the X-ray diffraction measurements ensure that the bulk crystalline I m m a structure is retained within the nanoparticles, thanks to the employed low milling times ranging from t = 0.5 to t = 5 h. The analysis of the magnetic measurements shows a crossover from Superantiferromagnetism (SAF) to a Super Spin Glass state as the size decreases at NP size of 〈 D 〉 ≈ 18 nm. The microstrain contribution, which is always kept below 1%, together with the increasing surface-to-core ratio of the magnetic moments, trigger the magnetic disorder. Additionally, an extra contribution to the magnetic disorder is revealed within the SAF state, as the oscillating RKKY indirect exchange achieves to couple with the aforementioned contribution that emerges from the size reduction. The combination of both sources of disorder leads to a maximised frustration for 〈 D 〉 ≈ 25 nm sized NPs.

Breakdown of the coherence effects and Fermi liquid behavior in YbAl3 nanoparticles.

A change in the Kondo lattice behavior of bulk YbAl3 has been observed when the alloy is shaped into nanoparticles (≈12 nm). Measurements of the electrical resistivity show inhibited coherence effects and deviation from the standard Fermi liquid behavior (T 2-dependence). These results are interpreted as being due to the effect of the disruption of the periodicity of the array of Kondo ions provoked by the size reduction process. Additionally, the ensemble of randomly placed nanoparticles also triggers an extra source of electronic scattering at very low temperatures (≈15 K) due to quantum interference effects.

Magnetic phase diagram of superantiferromagnetic TbCu2 nanoparticles.

The structural state and static and dynamic magnetic properties of TbCu2 nanoparticles are reported to be produced by mechanical milling under inert atmosphere. The randomly dispersed nanoparticles as detected by TEM retain the bulk symmetry with an orthorhombic Imma lattice and Tb and Cu in the 4e and 8h positions, respectively. Rietveld refinements confirm that the milling produces a controlled reduction of particle sizes reaching ≃6 nm and an increase of the microstrain up to ≃0.6%. The electrical resistivity indicates a metallic behavior and the presence of a magnetic contribution to the electronic scattering which decreases with milling times. The dc-susceptibility shows a reduction of the Néel transition (from 49 K to 43 K) and a progressive increase of a peak (from 9 K to 15 K) in the zero-field-cooled magnetization with size reduction. The exchange anisotropy is very weak (a bias field of ≃30 Oe) and is due to the presence of a disordered (thin) shell coupled to the antiferromagnetic core. The dynamic susceptibility evidences a critical slowing down in the spin-disordered state for the lowest temperature peak associated with a spin glass-like freezing with a tendency of zv and ß exponents to increase when the size becomes 6 nm (zv ≃ 6.6 and ß ≃ 0.85). A Rietveld analysis of the neutron diffraction patterns 1.8 ≤ T ≤ 60 K, including the magnetic structure determination, reveals that there is a reduction of the expected moment (≃80%), which must be connected to the presence of the disordered particle shell. The core magnetic structure retains the bulk antiferromagnetic arrangement. The overall interpretation is based on a superantiferromagnetic behavior which at low temperatures coexists with a canting of surface moments and a mismatch of the antiferromagnetic sublattices of the nanoparticles. We propose a novel magnetic phase diagram where changes are provoked by a combination of the decrease of size and the increase of microstrain.

Magnetic properties of TbAl2 nanometric alloys.

The magnetic properties of nanometric TbAI2 alloys have been investigated. The Curie temperature (T(c)) of these nanometric alloys is strongly size dependent and decreases from 103 K for the bulk alloy down to 98 K for the 14 nm alloy, as the particle volume is reduced. This reduction of T(c) has been explained by a finite-size scaling law of type [T(c)(D) -T(c)(infinity)]/T(c)(infinity) = -(D/D0)-(1/vp), with v = 0.7 and D0 = 2.2a (a, the lattice parameter), in agreement with the three-dimensional Heisenberg model. The size dependence of the coercivity has also been established. An increase of the coercivity from 0.08 kOe (bulk) to 1 kOe for 10 h milled alloy, indicates the crossover from multidomain to single domain behavior around 85 nm, as expected from the estimate of the critical size of monodomain particles. The field dependence of the magnetization indicates a faster thermal reduction of the magnetization of the nanosized alloys (17% in 300 h milled alloy with mean particle size of 14 nm) related to the bulk (3%), in the temperature range between 5 K and 30 K. The results can be explained as a direct consequence of the competing effects of the surface and the purely finite-size effects, in an ensemble of nanometric particles suffering interactions.

Poly(methyl methacrylate) coating of soft magnetic amorphous and crystalline Fe,Co-B nanoparticles by chemical reduction.

The structural and magnetic properties of a collection of nanoparticles coated by Poly(methyl methacrylate) through a wet chemical synthesis have been investigated. The particles display either an amorphous (M = Fe, Co) M-B arrangement or a mixed structure bcc-Fe and fcc-Co + amorphous M-B. Both show the presence of a metal oxi-hydroxide formed in aqueous reduction. The organic coating facilitates technological handling. The cost-effective synthesis involves a reduction in a Poly(methyl methacrylate) aqueous solution of iron(II) or cobalt(II) sulphates (< 0.5 M) by sodium borohydride (< 0.5 M). The particles present an oxidized component, as deduced from X-ray diffraction, Mössbauer and Fe- and Co K-edge X-ray absorption spectroscopy and electron microscopy. For the ferrous alloys, this Fe-oxide is alpha-goethite, favoured by the aqueous solution. The Poly(methyl methacrylate) coating is confirmed by Fourier transform infrared spectroscopy. In pure amorphous core alloys there is a drastic change of the coercivity from bulk to around 30 Oe in the nanoparticles. The mixed structured alloys also lie in the soft magnetic regime. Magnetisation values at room temperature range around 100 emu/g. The coercivity stems from multidomain particles and their agglomeration, triggering the dipolar interactions.

Phonon softening on the specific heat of nanocrystalline metals.

Specific heat enhancement in several common nanocrystalline metals is established by comparison with their bulk counterparts. Measurements were carried out in Fe, Cu, Ni and binary alloy LaAl(2). The excess specific heat is evidenced as a low temperature peak below 65 K and a high temperature slope above 150 K. The experimental data are in good agreement with a model which considers contributions from the grain boundary and core atoms in the nanoparticles. This model is supported by Raman spectroscopy measurements, showing a softening of the frequency phonon modes associated with a size reduction and increase of the atomic disorder.

Long-range magnetic ordering in magnetic ionic liquid: Emim[FeCl4].

Up to now most of the magnetic ionic liquids containing tetrachloroferrate ion FeCl(4) have evidenced a paramagnetic temperature dependence of the magnetic susceptibility, with only small deviations from the Curie law at low temperatures. However, we report on the physical properties of 1-ethyl-3-methylimidazolium tetrachloroferrate Emim[FeCl(4)], that clearly shows a long-range antiferromagnetic ordering below the Néel temperature T(N)≈3.8 K. In addition, the field dependence of the magnetization measured at 2 K is characterized by a linear behaviour up to around 40 kOe, while above this field the magnetization becomes saturated with a value of 4.3 µ(B)/Fe, which is near the expected fully saturated value of 5 µ(B)/Fe for an Fe(3+) ion.

Influence of pressure on the magnetic ordering of CeNiSnH and CeNiSnH(1.8) hydrides.

The magnetic properties of the antiferromagnet CeNiSnH and of the ferromagnet CeNiSnH(1.8) on hydrostatic pressure (0≤P≤10.8 bar) have been determined using a miniature piston-cylinder CuBe pressure cell. With increasing P, the Néel temperature of CeNiSnH increases weakly from 4.77 to 5.01 K whereas the Curie temperature of CeNiSnH(1.8) decreases rapidly from 7.16 to 5.30 K. Similar pressure dependence is also observed in the critical field of the metamagnetic transition of CeNiSnH and in the coercive field of CeNiSnH(1.8). Electronic structure calculations for these hydrides within the density functional theory show agreement with the experimental findings. Detailed examination of the chemical bonding features point to the conclusion that the antibonding Ce-Ni states below the Fermi level for CeNiSnH(1.8) could be responsible for the decrease of its Curie temperature under applied pressure.

Size effects in the magnetic behaviour of TbAl(2) milled alloys.

The study of the magnetic properties depending upon mechanical milling of the ferromagnetic polycrystalline TbAl(2) material is reported. Rietveld analysis of the x-ray diffraction data reveals a decrease in the grain size down to 14 nm and a -0.15% variation in the lattice parameter, after 300 h of milling time. Irreversibility in the zero field cooled-field cooled (ZFC-FC) dc susceptibility and clear peaks in the ac susceptibility between 5 and 300 K show that the long-range ferromagnetic structure is inhibited in favour of a disordered spin arrangement below 45 K. This glassy behaviour is also deduced from the variation of the irreversibility transition with the field (H(2/3)) and frequency. The magnetization process of the bulk TbAl(2) is governed by domain-wall thermal activation processes. In contrast, in the milled samples, cluster-glass properties arise as a result of cooperative interactions due to the substitutional disorder. The interactions are also influenced by the nanograin structure of the milled alloys, showing a variation in coercivity with the grain size, below the crossover between the multi- and single-domain behaviours.

Polymorphic Alu insertions among Mayan populations.

The Mayan homeland within Mesoamerica spans five countries: Belize, El Salvador, Guatemala, Honduras and Mexico. There are indications that the people we call the Maya migrated from the north to the highlands of Guatemala as early as 4000 B.C. Their existence was village-based and agricultural. The culture of these Preclassic Mayans owes much to the earlier Olmec civilization, which flourished in the southern portion of North America. In this study, four different Mayan groups were examined to assess their genetic variability. Ten polymorphic Alu insertion (PAI) loci were employed to ascertain the genetic affinities among these Mayan groups. North American, African, European and Asian populations were also examined as reference populations. Our results suggest that the Mayan groups examined in this study are not genetically homogeneous.