Trends of Axillary Treatment in Sentinel Node-Positive Breast Cancer Patients Undergoing Mastectomy

Background: The ACOSOG-Z0011- and the AMAROS-trial obviated the need for axillary surgery in most sentinel node-positive (SLN+) breast cancer patients undergoing breast-conserving surgery (BCS). Data for patients who undergo mastectomy is scarce. The purpose of this study was to investigate patterns of axillary treatment in SLN+ patients treated by mastectomy in the years after the publication of landmark studies regarding axillary treatment in SLN+ breast cancer patients undergoing BCS. Methods: This was a population-based study in cT1-3N0M0 breast cancer patients treated by mastectomy and staged as SLN+ between 2009 and 2018. The performance of an axillary lymph node dissection (ALND) and/or administration of postmastectomy radiotherapy (PMRT) were primary outcomes and were studied over time. Results: The study included 10,633 patients. The frequency of ALND performance decreased from 78% in 2009 to 10% in 2018, whereas PMRT increased from 4 to 49% (P < 0.001). In ≥N1a patients, ALND performance decreased from 93 to 20%, whereas PMRT increased to 70% (P < 0.001). In N1mi and N0itc patients, ALND was abandoned during the study period, whereas PMRT increased to 38% and 13% respectively (P < 0.001), respectively. Age, tumor subtype, N-stage, and hospital type affected the likelihood that patients underwent ALND. Conclusions: In this study in SLN+ breast cancer patients undergoing mastectomy, use of ALND decreased drastically over time. By the end of 2018 most ≥N1a patients received PMRT as the only adjuvant axillary treatment, whereas the majority of N1mi and N0itc patients received no additional treatment

Patients’ perceptions of 70-gene signature testing: commonly changing the initial inclination to undergo or forego chemotherapy and reducing decisional conflict

PURPOSE: Little is known about the impact of 70-gene signature (70-GS) use on patients' chemotherapy decision-making. The primary aim of this study was to evaluate the impact of 70-GS use on patients' decisions to undergo chemotherapy. The perceived decision conflict during decision-making was a secondary objective of the study. METHODS: Patients operated for estrogen receptor positive early breast cancer were asked to fill out a questionnaire probing their inclination to undergo chemotherapy before deployment of the 70-GS test. After disclosure of the 70-GS result patients were asked about their decision regarding chemotherapy. Patients' decisional conflict was measured using the 16-item decisional conflict scale (DCS); scores  37.5 implies that one feels unsure about a choice. RESULTS: Between January 1th 2017 and December 31th 2018, 106 patients completed both questionnaires. Before deployment of the 70-GS, 58% of patients (n = 62) formulated a clear treatment preference, of whom 21 patients (34%) changed their opinion on treatment with chemotherapy following the 70-GS. The final decision regarding chemotherapy was in line with the 70-GS result in 90% of patients. The percentage of patients who felt unsure about their preference to be treated with chemotherapy decreased from 42 to 5% after disclosure of the 70-GS. The mean total DCS significantly decreased from pre-test to post-test from 35 to 23, irrespective of the risk estimate (p < 0.001). CONCLUSION: Deployment of the 70-GS changed patients' inclination to undergo adjuvant chemotherapy in one third of patients and decreased patients' decisional conflict

Design of the ExCersion-VCI study: The effect of aerobic exercise on cerebral perfusion in patients with vascular cognitive impairment

There is evidence for a beneficial effect of aerobic exercise on cognition, but underlying mechanisms are unclear. In this study, we test the hypothesis that aerobic exercise increases cerebral blood flow (CBF) in patients with vascular cognitive impairment (VCI). This study is a multicenter single-blind randomized controlled trial among 80 patients with VCI. Most important inclusion criteria are a diagnosis of VCI with Mini-Mental State Examination ≥22 and Clinical Dementia Rating ≤0.5. Participants are randomized into an aerobic exercise group or a control group. The aerobic exercise program aims to improve cardiorespiratory fitness and takes 14 weeks, with a frequency of three times a week. Participants are provided with a bicycle ergometer at home. The control group receives two information meetings. Primary outcome measure is change in CBF. We expect this study to provide insight into the potential mechanism by which aerobic exercise improves hemodynamic status

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M&gt;70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0&lt;e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Interplay between gene-expression profiling and adjuvant systemic treatment decision-making in early stage breast cancer patients

Adjuvant systemic treatment (AST) has improved outcome for breast cancer patients. However, not every breast cancer patient benefits from AST. Therefore, clinical treatment guidelines have been developed to distinguish those patients in whom the benefits of AST outweigh the negative effects based on their clinicopathological profile. In the first part of this thesis we describe the increased use of AST in Dutch early stage breast cancer patients on a nation-wide level under the influence of evolving clinical treatment guidelines. Furthermore, we demonstrate that guidelines are not always followed and that especially undertreatment (i.e. not receiving AST despite a guideline recommendation) is common. Clinicopathological factors do not always accurately identify those patients in whom AST is beneficial. In recent years gene-expression profiles (GEPs) have been developed to better identify those patients in whom AST is beneficial. In the second part of this thesis we describe how GEPs are currently deployed, the impact on the administration of adjuvant chemotherapy and chemotherapy decision-making in early stage breast cancer patients on a nationwide level. Concurrent with the introduction of GEPs in clinical practice, four molecular subtypes of breast cancer were identified which are associated with breast cancer outcome. These subtypes are increasingly used in the AST decision-making process. Pathological assessment of hormone receptor status, Ki67 status and Her2-Neu status can be used as a surrogate to distinguish between these molecular subtypes. In the last part of this thesis reveal a high discrepancy between molecular subtyping based on pathological assessment or a gene-expression test

Interplay between gene-expression profiling and adjuvant systemic treatment decision-making in early stage breast cancer patients

Adjuvant systemic treatment (AST) has improved outcome for breast cancer patients. However, not every breast cancer patient benefits from AST. Therefore, clinical treatment guidelines have been developed to distinguish those patients in whom the benefits of AST outweigh the negative effects based on their clinicopathological profile. In the first part of this thesis we describe the increased use of AST in Dutch early stage breast cancer patients on a nation-wide level under the influence of evolving clinical treatment guidelines. Furthermore, we demonstrate that guidelines are not always followed and that especially undertreatment (i.e. not receiving AST despite a guideline recommendation) is common. Clinicopathological factors do not always accurately identify those patients in whom AST is beneficial. In recent years gene-expression profiles (GEPs) have been developed to better identify those patients in whom AST is beneficial. In the second part of this thesis we describe how GEPs are currently deployed, the impact on the administration of adjuvant chemotherapy and chemotherapy decision-making in early stage breast cancer patients on a nationwide level. Concurrent with the introduction of GEPs in clinical practice, four molecular subtypes of breast cancer were identified which are associated with breast cancer outcome. These subtypes are increasingly used in the AST decision-making process. Pathological assessment of hormone receptor status, Ki67 status and Her2-Neu status can be used as a surrogate to distinguish between these molecular subtypes. In the last part of this thesis reveal a high discrepancy between molecular subtyping based on pathological assessment or a gene-expression test