Cancer drug related cardiotoxicity during breast cancer treatment

Introduction: Breast cancer (BC) is the most common cancer in women. Although therapeutic armamentarium like chemotherapy, endocrine and target agents have increased survival, cardiovascular side effects have been observed. A comprehensive risk assessment, early detection and management of cardiac adverse events is therefore needed. Areas covered: In this review we focus on cardiotoxicity data deriving from Phase III randomized trials, systematic reviews and meta-analysis in BC patients. We provide insight into advances that have been made in the molecular mechanisms, clinical presentation and management of such adverse event. Expert opinion: Despite the large number of data from Phase III trials about cardiac events incidence, there are poor evidences for detection, monitoring and management of cardiotoxicity during BC treatment. Future cardiotoxicity-oriented clinical cancer research can help to predict the risk of cardiac adverse events and improve patients’ outcome. Multidisciplinary approach as well as integration of blood biomarkers with imaging will be desirable

Experimental removals reveal dietary niche partitioning facilitates coexistence between native and introduced species

Niche overlap between native species and ecologically similar invaders can lead to competitive exclusion of threatened native species, but if two such species also co-occur naturally elsewhere, interactions between native and introduced populations may mirror coevolved niche partitioning that reduces competition and promotes coexistence.A single, insular population of Fremont's squirrel (Tamiasciurus fremonti) the Mount Graham red squirrel (MGRS; T. f. grahamensis) in the Pinaleño Mountains, Arizona, USA, is critically endangered and resource competition with introduced Abert's squirrels (Sciurus aberti) may threaten its long-term persistence. The species are naturally synoptic in other mountain sites, and both consume diets comprised primarily of conifer seeds and fungi.We conducted experimental removals of introduced Abert's squirrels and used stable isotope analysis of diets before and after removals, and of diets in naturally syntopic populations to test the hypothesis that dietary niche partitioning can facilitate coexistence between native and introduced species. We also developed a novel approach to determine the influence of fluctuating food availability on carbon enrichment in consumers.Mount Graham red squirrels and introduced Abert's squirrels partitioned the dietary niche similarly to naturally syntopic populations. Removals had no apparent effect. Diet of MGRS was more closely linked to availability of resources than to presence of Abert's squirrels.Flexible dietary niche of introduced Abert's squirrels may have allowed them to exploit a resource opportunity in syntopy with MGRS. Variable food production of MGRS habitat may intensify competition in poor years, and territorial defense against non-native Abert's squirrels likely imposes fitness costs on individual MGRS. Similarity in our model species' diets may make MGRS more vulnerable to competition if climate change eliminates the advantages of larder-hoarding. Where introduced populations of ecologically similar species are better adapted to changing conditions, they may ultimately replace southern peripheral populations of native species.USDA Forest Service; American Society of Mammalogists Grant in Aid of Research; T&E Inc. Grants for Conservation Biology; University of Arizona; Arizona Game and Fish DepartmentOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Key 19^{19}Ne states identified affecting γ\gamma-ray emission from 18^{18}F in novae

Detection of nuclear-decay $\gamma$ rays provides a sensitive thermometer of nova nucleosynthesis. The most intense $\gamma$-ray flux is thought to be annihilation radiation from the $\beta^+$ decay of $^{18}$F, which is destroyed prior to decay by the $^{18}$F($p$,$\alpha$)$^{15}$O reaction. Estimates of $^{18}$F production had been uncertain, however, because key near-threshold levels in the compound nucleus, $^{19}$Ne, had yet to be identified. This Letter reports the first measurement of the $^{19}$F($^{3}$He,$t\gamma$)$^{19}$Ne reaction, in which the placement of two long-sought 3/2$^+$ levels is suggested via triton-$\gamma$-$\gamma$ coincidences. The precise determination of their resonance energies reduces the upper limit of the rate by a factor of $1.5-17$ at nova temperatures and reduces the average uncertainty on the nova detection probability by a factor of 2.1.Comment: 6 pages, 4 figure

First Measurement of Coherent Elastic Neutrino-Nucleus Scattering on Argon

We report the first measurement of coherent elastic neutrino-nucleus scattering (\cevns) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two independent analyses prefer \cevns over the background-only null hypothesis with greater than $3\sigma$ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2 $\pm$ 0.7) $\times$10$^{-39}$ cm$^2$ -- consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the \cevns process and provides improved constraints on non-standard neutrino interactions.Comment: 8 pages, 5 figures with 2 pages, 6 figures supplementary material V3: fixes to figs 3,4 V4: fix typo in table 1, V5: replaced missing appendix, V6: fix Eq 1, new fig 3, V7 final version, updated with final revision

New γ\gamma-ray Transitions Observed in 19^{19}Ne with Implications for the 15^{15}O(α\alpha,γ\gamma)19^{19}Ne Reaction Rate

The $^{15}$O($\alpha$,$\gamma$)$^{19}$Ne reaction is responsible for breakout from the hot CNO cycle in Type I x-ray bursts. Understanding the properties of resonances between $E_x = 4$ and 5 MeV in $^{19}$Ne is crucial in the calculation of this reaction rate. The spins and parities of these states are well known, with the exception of the 4.14- and 4.20-MeV states, which have adopted spin-parities of 9/2$^-$ and 7/2$^-$, respectively. Gamma-ray transitions from these states were studied using triton-$\gamma$-$\gamma$ coincidences from the $^{19}$F($^{3}$He,$t\gamma$)$^{19}$Ne reaction measured with GODDESS (Gammasphere ORRUBA Dual Detectors for Experimental Structure Studies) at Argonne National Laboratory. The observed transitions from the 4.14- and 4.20-MeV states provide strong evidence that the $J^\pi$ values are actually 7/2$^-$ and 9/2$^-$, respectively. These assignments are consistent with the values in the $^{19}$F mirror nucleus and in contrast to previously accepted assignments

Phase II study of sequential hormonal therapy with anastrozole/exemestane in advanced and metastatic breast cancer

Hormonal therapy is the preferred systemic treatment for recurrent or metastatic, post-menopausal hormone-receptor-positive breast cancer. Previous studies have shown that there is no cross-resistance between exemestane and reversible aromatase inhibitors. Exposure to hormonal therapy does not hamper later response to chemotherapy. Patients with locally advanced or metastatic, hormonal receptor positive or unknown, breast cancer were treated with oral anastrozole, until disease progression, followed by oral exemestane until new evidence of disease progression. The primary end point of the study was clinical benefit, defined as the sum of complete responses (CR), partial responses (PR) and > 24 weeks stable disease (SD). In all, 100 patients were enrolled in the study. Anastrozole produced eight CR and 19 PR for an overall response rate of 27% (95% CI: 18.6-36.8%). An additional 46 patients had long-term (> 24 weeks) SD for an overall clinical benefit of 73% (95% CI: 63.2-81.4). Median time to progression (TTP) was 11 months (95% CI: 10-12). A total of 50 patients were evaluated for the second-line treatment: exemestane produced one CR and three PR; 25 patients had SD which lasted ≥ 6 months in 18 patients. Median TTP was 5 months. Toxicity of treatment was low. Our study confirms that treatment with sequential hormonal agents can extend the period of time during which endocrine therapy can be used, thereby deferring the decision to use chemotherapy. © 2005 Cancer Research UK

Knowledge and attitudes towards clinical trials among women with ovarian cancer: results of the ACTO study

Background: Despite several initiatives by research groups, regulatory authorities, and scientific associations to engage citizens/patients in clinical research, there are still obstacles to participation. Among the main discouraging aspects are incomplete understanding of the concepts related to a clinical trial, and the scant, sometimes confused, explanations given. This observational, cross-sectional multicenter study investigated knowledge, attitudes and trust in clinical research. We conducted a survey among women with ovarian cancer at their first follow-up visit or first therapy session, treated in centers belonging to the Mario Negri Gynecologic Oncology (MaNGO) and Multicenter Italian Trials in Ovarian Cancer (MITO) groups. A questionnaire on knowledge, attitudes and experience was assembled ad hoc after a literature review and a validation process involving patients of the Alliance against Ovarian Cancer (ACTO). Results: From 25 centers 348 questionnaire were collected; 73.5% of responders were 56 years or older, 54.8% had a high level of education, more than 80% had no experience of trial participation. Among participants 59% knew what clinical trials were and 71% what informed consent was. However, more than half did not know the meaning of the term randomization. More than half (56%) were in favor of participating in a clinical trial, but 35% were not certain. Almost all responders acknowledged the doctor’s importance in decision-making. Patients’ associations were recognized as having a powerful role in the design and planning of clinical trials. Conclusions: This study helps depict the knowledge and attitudes of women with ovarian cancer in relation to clinical trials, suggesting measures aimed at improving trial “culture”, literacy and compliance, and fresh ways of communication between doctors and patients

Dose intensity and efficacy of the combination of everolimus and exemestane (EVE/EXE) in a real-world population of hormone receptor-positive (ER+/PgR+), HER2-negative advanced breast cancer (ABC) patients: a multicenter Italian experience

Aim: This retrospective analysis focused on the effect of treatment with EVE/EXE in a real-world population outside of clinical trials. We examined the efficacy of this combination in terms of PFS and RR related to dose intensity (5 mg daily versus 10 mg daily) and tolerability. Methods: 163 HER2-negative ER+/PgR+ ABC patients, treated with EVE/EXE from May 2011 to March 2016, were included in the analysis. The primary endpoints were the correlation between the daily dose and RR and PFS, as well as an evaluation of the tolerability of the combination. Secondary endpoints were RR, PFS, and OS according to the line of treatment. Patients were classified into three different groups, each with a different dose intensity of everolimus (A, B, C). Results: RR was 29.8% (A), 27.8% (B) (p = 0.953), and not evaluable (C). PFS was 9 months (95% CI 7–11) (A), 10 months (95% CI 9–11) (B), and 5 months (95% CI 2–8) (C), p = 0.956. OS was 38 months (95% CI 24–38) (A), median not reached (B), and 13 months (95% CI 10–25) (C), p = 0.002. Adverse events were stomatitis 57.7% (11.0% grade 3–4), asthenia 46.0% (6.1% grade 3–4), hypercholesterolemia 46.0% (0.6% grade 3–4), and hyperglycemia 35.6% (5.5% grade 3–4). The main reason for discontinuation/interruption was grade 2–3 stomatitis. Conclusions: No correlation was found between dose intensity (5 vs. 10 mg labeled dose) and efficacy in terms of RR and PFS. The tolerability of the higher dose was poor in our experience, although this had no impact on efficacy

Investigation of Compton scattering for gamma beam intensity measurements and perspectives at ELI-NP

Compton γ-ray sources have been in operation for over 30 years with new facilities being under construction or proposed. The gamma beam system under implementation at the Extreme Light Infrastructure - Nuclear Physics facility in Romania will deliver brilliant γ-ray beams with energies up to 19.5 MeV. Several instruments for measuring the parameters of the γ-ray beam are under development at ELI-NP. One of these instruments based on a High Purity Germanium detector is routinely used for beam energy measurements at other facilities. Here we investigate the use of a High Purity Germanium detector to continuously monitor the intensity of the ELI-NP gamma beam by measuring the inelastic scattering of photons. This method relies on both experimental and simulated data and it has been successfully tested during a recent experiment at the High Intensity γ-ray Source facility