Acute toxicity of intraoperative radiotherapy and external beam-accelerated partial breast irradiation in elderly breast cancer patients

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Sustainable innovation through commitment and engagement: The example of SunFuel

Sustainable innovation is to satisfy not only customers’ needs and the innovating firm’s goals, it also should meet social and environmental targets. These manifold requirements lead to increased complexity and risk, often making collaboration amongst firms necessary. However, multiple targets and multiple partners may threaten enduring commitment to the innovation. Therefore, our research question is, how to manage a firm’s own commitment and promote its partners’ commitment to a sustainable innovation. This is particularly relevant if several technological paths exist because firms’ histories and present states differ and thus companies may come to favour alternative solutions.\ud For a company intending to invest into a sustainable solution it is not only important to assess its own competencies and interests but also to understand the partners’ positions vis-à-vis the innovation. We propose: First, at an early stage, when selecting a technological path, to screen three levels of influence on partners’ strategies: firm's competencies & orientation, industry background and regulatory system and Second, to engage with partners continuously, taking changing perceptions and interests into account. SunFuel is used as an example to demonstrate the usefulness of our framework

Single dose IOERT versus whole breast irradiation

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Health-related quality of life of breast cancer patients after accelerated partial breast irradiation using intraoperative or external beam radiotherapy technique

Purpose: To compare health-related quality of life (HRQL) in elderly breast cancer patients between two types of Accelerated Partial Breast Irradiation: intraoperative radiotherapy (IORT) and external beam APBI (EB-APBI).Methods: Between 2011 and 2016 women >= 60 years undergoing breast conserving therapy for early stage breast cancer were included in a prospective multi-centre cohort study. Patients were treated with electron IORT (1 x 23.3 Gy) or photon EB-APBI (10 x 3.85 Gy daily). HRQL was measured by the EORTC-QLQ C30 and BR23 questionnaires before surgery and at several time points until 1 year.Results: HRQoL data was available of 204 IORT and 158 EB-APBI patients. In longitudinal analyses emotional functioning and future perspective were significantly, but not clinically relevantly, worse in IORT-treated patients, and improved significantly during follow-up in both groups. All other aspects of HRQL slightly worsened after treatment and recovered within 3 months with an improvement until 1 year. Cross-sectional analysis showed that postoperatively fatigue and role functioning were significantly worse in IORT patients compared to EB-APBI patients who were not yet irradiated, but the difference was not clinically relevant. At other timepoints there were no significant differences. Multivariable analysis at 1 year identified comorbidity and systemic therapy as risk factors for a worse global health score (GHS).Conclusions: EB-APBI and IORT were well tolerated. Despite a temporary deterioration after treatment, all HRQL scales recovered within 3 months resulting in no clinically relevant differences until 1 year between groups nor compared to baseline levels. (C) 2019 Elsevier Ltd. All rights reserved.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

SAFESTEREO: phase II randomized trial to compare stereotactic radiosurgery with fractionated stereotactic radiosurgery for brain metastases

Background: Stereotactic radiosurgery (SRS) is a frequently chosen treatment for patients with brain metastases and the number of long-term survivors is increasing. Brain necrosis (e.g. radionecrosis) is the most important long-term side effect of the treatment. Retrospective studies show a lower risk of radionecrosis and local tumor recurrence after fractionated stereotactic radiosurgery (fSRS, e.g. five fractions) compared with stereotactic radiosurgery in one or three fractions. This is especially true for patients with large brain metastases. As such, the 2022 ASTRO guideline of radiotherapy for brain metastases recommends more research to fSRS to reduce the risk of radionecrosis. This multicenter prospective randomized study aims to determine whether the incidence of adverse local events (either local failure or radionecrosis) can be reduced using fSRS versus SRS in one or three fractions in patients with brain metastases. Methods: Patients are eligible with one or more brain metastases from a solid primary tumor, age of 18 years or older, and a Karnofsky Performance Status ≥ 70. Exclusion criteria include patients with small cell lung cancer, germinoma or lymphoma, leptomeningeal metastases, a contraindication for MRI, prior inclusion in this study, prior surgery for brain metastases, prior radiotherapy for the same brain metastases (in-field re-irradiation). Participants will be randomized between SRS with a dose of 15–24 Gy in 1 or 3 fractions (standard arm) or fSRS 35 Gy in five fractions (experimental arm). The primary endpoint is the incidence of a local adverse event (local tumor failure or radionecrosis identified on MRI scans) at two years after treatment. Secondary endpoints are salvage treatment and the use of corticosteroids, bevacizumab, or antiepileptic drugs, survival, distant brain recurrences, toxicity, and quality of life. Discussion: Currently, limiting the risk of adverse events such as radionecrosis is a major challenge in the treatment of brain metastases. fSRS potentially reduces this risk of radionecrosis and local tumor failure. Trial registration: ClincalTrials.gov, trial registration number: NCT05346367, trial registration date: 26 April 2022