Abstract of papers for full membership at the Royal Belgian Society of Radiology

Introduction: In up to 30% of patients with epilepsy, the disease becomes refractory to antiepileptic drugs or the side effects of the medications are intolerable. These patients may be referred for surgical resection. Patients with refractory epilepsy in whom the epileptogenic zone cannot be precisely identified using the currently available presurgical evaluation tools are not likely to undergo resective surgery and remain prone to uncontrolled seizures. The aim of this study is to assess the added value of surface coil imaging at 3-Tesla (3T SCI) with regard to their potential to locate the epiloptogenic zone in order to increase the number of patients eligible for resective surgery

A phase 1 study of mTORC1/2 inhibitor BI 860585 as a single agent or with exemestane or paclitaxel in patients with advanced solid tumors

This phase 1 trial (NCT01938846) determined the maximum tolerated dose (MTD) of the mTOR serine/threonine kinase inhibitor, BI 860585, as monotherapy and with exemestane or paclitaxel in patients with advanced solid tumors. This 3+3 dose-escalation study assessed BI 860585 monotherapy (5–300 mg/day; Arm A), BI 860585 (40–220 mg/day; Arm B) with 25 mg/day exemestane, and BI 860585 (80–220 mg/day; Arm C) with 60–80 mg/m2 /week paclitaxel, in 28-day cycles. Primary endpoints were the number of patients with dose-limiting toxicities (DLTs) in cycle 1 and the MTD. Forty-one, 25, and 24 patients were treated (Arms A, B, and C). DLTs were observed in four (rash (n = 2), elevated alanine aminotransferase/aspartate aminotransferase, diarrhea), four (rash (n = 3), stomatitis, and increased gamma-glutamyl transferase), and two (diarrhea, increased blood creatine phosphokinase) patients in cycle 1. The BI 860585 MTD was 220 mg/day (Arm A) and 160 mg/day (Arms B and C). Nine patients achieved an objective response (Arm B: Four partial responses (PRs); Arm C: Four PRs; one complete response). The disease control rate was 20%, 28%, and 58% (Arms A, B, and C). The most frequent treatment-related adverse events (AEs) were hyperglycemia (54%) and diarrhea (39%) (Arm A); diarrhea (40%) and stomatitis (40%) (Arm B); fatigue (58%) and diarrhea (58%) (Arm C). The MTD was determined in all arms. Antitumor activity was observed with BI 860585 monotherapy and in combination with exemestane or paclitaxel

Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors

BackgroundDesmoid tumors are rare, locally aggressive, highly recurrent soft-tissue tumors without approved treatments.MethodsWe conducted a phase 3, international, double-blind, randomized, placebo-controlled trial of nirogacestat in adults with progressing desmoid tumors according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were assigned in a 1:1 ratio to receive the oral γ-secretase inhibitor nirogacestat (150 mg) or placebo twice daily. The primary end point was progression-free survival. ResultsFrom May 2019 through August 2020, a total of 70 patients were assigned to receive nirogacestat and 72 to receive placebo. Nirogacestat had a significant progression-free survival benefit over placebo (hazard ratio for disease progression or death, 0.29; 95% confidence interval, 0.15 to 0.55; PConclusionsNirogacestat was associated with significant benefits with respect to progression-free survival, objective response, pain, symptom burden, physical functioning, role functioning, and health-related quality of life in adults with progressing desmoid tumors. Adverse events with nirogacestat were frequent but mostly low grade. (Funded by SpringWorks Therapeutics; DeFi ClinicalTrials.gov number, NCT03785964.)Experimentele farmacotherapi

Influence of grain size on the electrochemical behavior of pure copper

Despite numerous research works a thorough understanding on how grain size influences the electrochemical behavior of metals is still lacking due to the inability to decouple grain size effects from other microstructural characteristics. In this work, the combination of potentiodynamic polarization measurements and the gold-nanoplating technique was used on high purity copper to further explore this relationship. The high purity copper was thermomechanically processed in such a way that three samples were produced with markedly different average grain sizes, namely 1.4, 48 and 191 A mu m. All other parameters influencing the electrochemical behavior, such as internal stresses and texture were kept constant; microstructural characterization was performed by electron backscatter diffraction. In 0.1 M HCl, the anodic polarization curves demonstrate that for the smaller the grain size a lower corrosion potential and higher corrosion current density is observed. The gold-nanoplating experiments show that the material with the smallest grain size is corroding more uniformly than the samples with the larger grain sizes. In the sample with the medium grain size, the higher electrochemical activity of the grain boundaries is demonstrated. In the largest grain size sample, both the grain boundaries as well as some of the grain interiors are covered with gold

Advance care planning - Family carer psychological distress and involvement in decision making:The ACTION trial

Objectives: Facilitated advance care planning (ACP) helps family carers' to be aware of patient preferences. It can improve family carers' involvement in decision making and their overall experiences at the end of life, as well as, reduce psychological stress. We investigated the effects of the ACTION Respecting Choices (RC) ACP intervention on the family carers' involvement in decision making in the last 3 months of the patients' life and on the family carers' psychological distress after 3 months of bereavement. Methods: Over six European countries, a sample of 162 bereaved family carers returned a bereavement questionnaire. Involvement in decision making was measured with a single item of the Views of Informal Carers-Evaluation of Services Short Form questionnaire. Psychological distress was measured with the Impact of Event Scale (IES). Results: No significant effect was found on family carers involvement in decision making in the last 3 months of the patients' life (95% CI 0.449 to 4.097). However, the probability of involvement in decision making was slightly higher in the intervention arm of the study (89.6% vs 86.7%; OR=1.357). Overall, no statistical difference was found between intervention and control group regarding the IES (M=34.1 (1.7) vs 31.8 (1.5); (95% CI -2.2 to 6.8)). Conclusion: The ACTION RC ACP intervention showed no significant effect on family carers' involvement in decision making or on subsequent psychological distress. More research is needed about (1) how family carers can be actively involved in ACP-conversations and (2) how to prepare family carers on their role in decision making. Trial registration number: International Standard Randomised Controlled Trial Number ISRCTN17231

NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act. In. Sarc): a multicentre, phase 2-3, randomised, controlled trial

Background Pathological complete response to preoperative treatment in adults with soft-tissue sarcoma can be achieved in only a few patients receiving radiotherapy. This phase 2-3 trial evaluated the safety and efficacy of the hafnium oxide (HfO2) nanoparticle NBTXR3 activated by radiotherapy versus radiotherapy alone as a pre-operative treatment in patients with locally advanced soft-tissue sarcoma.Methods Act. In. Sarc is a phase 2-3 randomised, multicentre, international trial. Adults (aged = 18 years) with locally advanced soft-tissue sarcoma of the extremity or trunk wall, of any histological grade, and requiring preoperative radiotherapy were included. Patients had to have a WHO performance status of 0-2 and a life expectancy of at least 6 months. Patients were randomly assigned (1:1) by an interactive web response system to receive either NBTXR3 (volume corresponding to 10% of baseline tumour volume at a fixed concentration of 53.3 g/L) as a single intratumoural administration before preoperative external-beam radiotherapy (50 Gy in 25 fractions) or radiotherapy alone, followed by surgery. Randomisation was stratified by histological subtype (myxoid liposarcoma vs others). This was an open-label study. The primary endpoint was the proportion of patients with a pathological complete response, assessed by a central pathology review board following European Organisation for Research and Treatment of Cancer guidelines in the intention-to-treat population full analysis set. Safety analyses were done in all patients who received at least one puncture and injection of NBTXR3 or at least one dose of radiotherapy. This study is registered with ClinicalTrials.gov, number NCT02379845, and is ongoing for long-term follow-up, but recruitment is complete.Findings Between March 3, 2015, and Nov 21, 2017, 180 eligible patients were enrolled and randomly assigned and 179 started treatment: 89 in the NBTXR3 plus radiotherapy group and 90 in the radiotherapy alone group. Two patients in the NBTXR3 group and one patient in the radiotherapy group were excluded from the efficacy analysis because they were subsequently discovered to be ineligible; thus, a total of 176 patients were analysed for the primary endpoint in the intention-to-treat full analysis set (87 in the NBTXR3 group and 89 in the radiotherapy alone group). A pathological complete response was noted in 14 (16%) of 87 patients in the NBTXR3 group and seven (8%) of 89 in the radiotherapy alone group (p=0.044). In both treatment groups, the most common grade 3-4 treatment-emergent adverse event was postoperative wound complication (eight [9%] of 89 patients in the NBTXR3 group and eight [9%] of 90 in the radiotherapy alone group). The most common grade 3-4 adverse events related to NBTXR3 administration were injection site pain (four [4%] of 89) and hypotension (four [4%]) and the most common grade 3-4 radiotherapy-related adverse event was radiation skin injury in both groups (five [6%] of 89 in the NBTXR3 group and four [4%] of 90 in the radiotherapy alone group). The most common treatment-emergent grade 3-4 adverse event related to NBTXR3 was hypotension (six [7%] of 89 patients). Serious adverse events were observed in 35 (39%) of 89 patients in the NBTXR3 group and 27 (30%) of 90 patients in the radiotherapy alone group. No treatment-related deaths occurred.Interpretation This trial validates the mode of action of this new class of radioenhancer, which potentially opens a large field of clinical applications in soft-tissue sarcoma and possibly other cancers. Copyright (C) 2019 Elsevier Ltd. All rights reserved.Molecular tumour pathology - and tumour geneticsMTG