Standard versus personalized schedule of regorafenib in metastatic gastrointestinal stromal tumors: a retrospective, multicenter, real-world study.

BACKGROUND: Despite its proven activity as third-line treatment in gastrointestinal stromal tumors (GIST), regorafenib can present a poor tolerability profile which often leads to treatment modifications and transient or permanent discontinuation; thus, in clinical practice physicians usually adopt various dosing and interval schedules to counteract regorafenib-related adverse events and avoid treatment interruption. The aim of this real-world study was to investigate the efficacy and safety of personalized schedules of regorafenib in patients with metastatic GIST, in comparison with the standard schedule (160 mg daily, 3-weeks-on, 1-week-off). PATIENTS AND METHODS: Institutional registries across seven Italian reference centers were retrospectively reviewed and data of interest retrieved to identify patients with GIST who had received regorafenib from February 2013 to January 2021. The Kaplan-Meier method was used to estimate survival and the log-rank test to make comparisons. RESULTS: Of a total of 152 patients with GIST, 49 were treated with standard dose, while 103 received personalized schedules. At a median follow-up of 36.5 months, median progression-free survival was 5.6 months [95% confidence interval (CI) 3.73-11.0 months] versus 9.7 months (95% CI 7.9-14.5 months) in the standard-dose and the personalized schedule groups, respectively [hazard ratio (HR) 0.51; 95% CI 0.34-0.75; P = 0.00052]. Median overall survival was 16.6 months (95% CI 14.1-21.8 months) versus 20.5 months (95% CI 15.0-25.4 months), respectively (HR 0.75; 95% CI 0.49-1.22; P = 0.16). CONCLUSIONS: Regorafenib-personalized schedules are commonly adopted in daily clinical practice of high-volume GIST expert centers and correlate with significant improvement of therapeutic outcomes. Therefore, regorafenib treatment optimization in patients with GIST may represent the best strategy to maximize long-term therapy.

A novel approach to medical radioisotope production using inverse kinematics: A successful production test of the theranostic radionuclide 67Cu.

A novel method for the production of important medical radioisotopes has been developed. The approach is based on performing the nuclear reaction in inverse kinematics, namely sending a heavy-ion beam of appropriate energy on a light target (e.g. H, d, He) and collecting the isotope of interest. In this work, as a proof-of-concept, we studied the production of the theranostic radionuclide 67Cu (T1/2 = 62 h) via the reaction of a 70Zn beam at 15 MeV/nucleon with a hydrogen gas target. The 67Cu radionuclide alongside other coproduced isotopes, was collected after the gas target on an aluminum catcher foil and their radioactivity was measured by off-line γ-ray analysis. After 36 h post irradiation, apart from the product of interest 67Cu, the main radioimpurity coming from the 70Zn + p reaction was 69mZn (T1/2 = 13.8 h), which can be reduced by further radio-cooling. Moreover, along with the radionuclide of interest produced in inverse kinematics, the production of additional radioisotopes is possible by making use of the forward-focused neutrons from the reaction and allowing them to interact with a secondary target. A preliminary successful test of this concept was realized in the present study. The main requirement to obtain activities appropriate for preclinical studies is the development of high-intensity heavy-ion primary beams.

Chemical modification of carbon nanomaterials (SWCNTs, DWCNTs, MWCNTs and SWCNHs) with diphenyl dichalcogenides.

Control over chemical functionalization is a crucial point in the field of nanotechnology. Herein, we present the covalent functionalization of several carbon nanoforms (single-walled carbon nanotubes, double-walled carbon nanotubes, multi-walled carbon nanotubes and carbon nanohorns) by means of diphenyl dichalcogenides. These ones show different reactivity to the nanomaterials and are able to modify their electronic properties depending on the electronegativity of the functionalizing heteroatom. Theoretical calculations were also performed to support the experimental results. All the modified structured nanocarbons were thoroughly characterized by TGA Raman, XPS, UV/Vis/nIR, IR and TEM techniques. Our findings propose a simple approach to functionalize carbon nanomaterials and, in the meantime, to tune their electronic properties.

Characterization of deuterium clusters mixed with helium gas for an application in beam-target-fusion experiments.

We measured the average deuterium cluster size within a mixture of deuterium clusters and helium gas by detecting Rayleigh scattering signals. The average cluster size from the gas mixture was comparable to that from a pure deuterium gas when the total backing pressure and temperature of the gas mixture were the same as those of the pure deuterium gas. According to these measurements, the average size of deuterium clusters depends on the total pressure and not the partial pressure of deuterium in the gas mixture. To characterize the cluster source size further, a Faraday cup was used to measure the average kinetic energy of the ions resulting from Coulomb explosion of deuterium clusters upon irradiation by an intense ultrashort pulse. The deuterium ions indeed acquired a similar amount of energy from the mixture target, corroborating our measurements of the average cluster size. As the addition of helium atoms did not reduce the resulting ion kinetic energies, the reported results confirm the utility of using a known cluster source for beam-target-fusion experiments by introducing a secondary target gas.

Experimental study of fusion neutron and proton yields produced by petawatt-laser-irradiated D2-³He or CD4-³He clustering gases.

We report on experiments in which the Texas Petawatt laser irradiated a mixture of deuterium or deuterated methane clusters and helium-3 gas, generating three types of nuclear fusion reactions: D(d,^{3}He)n, D(d,t)p, and ^{3}He(d,p)^{4}He. We measured the yields of fusion neutrons and protons from these reactions and found them to agree with yields based on a simple cylindrical plasma model using known cross sections and measured plasma parameters. Within our measurement errors, the fusion products were isotropically distributed. Plasma temperatures, important for the cross sections, were determined by two independent methods: (1) deuterium ion time of flight and (2) utilizing the ratio of neutron yield to proton yield from D(d,^{3}He)n and ^{3}He(d,p)^{4}He reactions, respectively. This experiment produced the highest ion temperature ever achieved with laser-irradiated deuterium clusters.

Measurement of the plasma astrophysical S factor for the 3He(d,p)4He reaction in exploding molecular clusters.

The plasma astrophysical S factor for the 3He(d,p)4He fusion reaction was measured for the first time at temperatures of few keV, using the interaction of intense ultrafast laser pulses with molecular deuterium clusters mixed with 3He atoms. Different proportions of D2 and 3He or CD4 and 3He were mixed in the gas target in order to allow the measurement of the cross section for the 3He(d,p)4He reaction. The yield of 14.7 MeV protons from the 3He(d,p)4He reaction was measured in order to extract the astrophysical S factor at low energies. Our result is in agreement with other S factor parametrizations found in the literature.

Temperature measurements of fusion plasmas produced by Petawatt-Laser-Irradiated D2 - (3)He or CD4 - (3)He clustering gases.

Two different methods have been employed to determine the plasma temperature in a laser-cluster fusion experiment on the Texas Petawatt laser. In the first, the temperature was derived from time-of-flight data of deuterium ions ejected from exploding D(2) or CD(4) clusters. In the second, the temperature was measured from the ratio of the rates of two different nuclear fusion reactions occurring in the plasma at the same time: D(d,(3)He)n and (3)He(d,p)(4)He. The temperatures determined by these two methods agree well, which indicates that (i) the ion energy distribution is not significantly distorted when ions travel in the disassembling plasma; (ii) the kinetic energy of deuterium ions, especially the "hottest part" responsible for nuclear fusion, is well described by a near-Maxwellian distribution.

Laboratory tests of low density astrophysical nuclear equations of state.

Clustering in low density nuclear matter has been investigated using the NIMROD multidetector at Texas A&M University. Thermal coalescence modes were employed to extract densities, ρ, and temperatures, T, for evolving systems formed in collisions of 47A MeV (40)Ar+(112)Sn, (124)Sn and (64)Zn+(112)Sn, (124)Sn. The yields of d, t, (3)He, and (4)He have been determined at ρ=0.002 to 0.03 nucleons/fm(3) and T=5 to 11 MeV. The experimentally derived equilibrium constants for α particle production are compared with those predicted by a number of astrophysical equations of state. The data provide important new constraints on the model calculations.

Experimental determination of in-medium cluster binding energies and Mott points in nuclear matter.

In-medium binding energies and Mott points for d, t, 3He and α clusters in low-density nuclear matter have been determined at specific combinations of temperature and density in low-density nuclear matter produced in collisions of 47A MeV 40Ar and 64Zn projectiles with 112Sn and 124Sn target nuclei. The experimentally derived values of the in-medium modified binding energies are in good agreement with recent theoretical predictions based upon the implementation of Pauli blocking effects in a quantum statistical approach.

Symmetry energy of dilute warm nuclear matter.

The symmetry energy of nuclear matter is a fundamental ingredient in the investigation of exotic nuclei, heavy-ion collisions, and astrophysical phenomena. New data from heavy-ion collisions can be used to extract the free symmetry energy and the internal symmetry energy at subsaturation densities and temperatures below 10 MeV. Conventional theoretical calculations of the symmetry energy based on mean-field approaches fail to give the correct low-temperature, low-density limit that is governed by correlations, in particular, by the appearance of bound states. A recently developed quantum-statistical approach that takes the formation of clusters into account predicts symmetry energies that are in very good agreement with the experimental data. A consistent description of the symmetry energy is given that joins the correct low-density limit with quasiparticle approaches valid near the saturation density.

Comment on "Observation of neutronless fusion reactions in picosecond laser plasmas".

The paper by Belyaev [Phys. Rev. E 72, 026406 (2005)] reported the first experimental observation of alpha particles produced in the thermonuclear reaction 11B(p,alpha)8Be induced by laser irradiation on a 11B polyethylene (CH2) composite target. The laser used in the experiment is characterized by a picosecond pulse duration and a peak of intensity of 2x10(18) W/cm(2). We suggest that both the background-reduction method adopted in their detection system and the choice of the detection energy region of the reaction products are possibly inadequate. Consequently the total yield reported underestimates the true yield. Based on their observation, we give an estimation of the total yield to be higher than their conclusion, i.e., of the order of 10(5)alpha per shot.

Quantum nature of a nuclear phase transition.

At finite temperatures and low densities, nuclei may undergo a phase change similar to a classical liquid-gas phase transition. Temperature is the control parameter while density and pressure are the conjugate variables. In the nucleus the difference between the proton and neutron concentrations acts as an additional order parameter, for which the symmetry potential is the conjugate variable. We present experimental results which reveal the N/Z dependence of the phase transition and discuss possible implications of these observations in terms of the Landau free energy description of critical phenomena.

Lyapunov exponents in unstable systems.

We investigate the dynamical behavior of unstable systems in the vicinity of the critical point associated with a liquid-gas phase transition. By considering a mean-field treatment, we first perform a linear analysis and discuss the instability growth times. Then, coming to complete Vlasov simulations, we investigate the role of nonlinear effects and calculate the Lyapunov exponents. As a main result, we find that near the critical point, the Lyapunov exponents exhibit a power-law behavior, with a critical exponent beta=0.5. This suggests that in thermodynamical systems the Lyapunov exponent behaves as an order parameter to signal the transition from the liquid to the gas phase.