Over the past decades, interest in second breast-conserving therapy (BCT) has increased due to, among others, advances in radiotherapy techniques. Preoperative partial breast irradiation (PBI) is an experimental treatment for patients with low-risk primary breast cancer. This approach can downstage the tumour and may possibly reduce toxicity and improve cosmetic outcomes compared with postoperative radiotherapy. This study aims to evaluate the feasibility of single-dose preoperative PBI and second breast-conserving surgery (BCS) for patients with an ipsilateral recurrent breast event (IRBE) after previous BCT.

The REPEAT trial is a multicentre, prospective, single-arm trial investigating ablative single-dose preoperative PBI in patients with an IRBE. Eligible patients are ≥50 years, have a unifocal non-lobular invasive breast cancer ≤2 cm, Bloom-Richardson grade 1 or 2, oestrogen receptor-positive, human epidermal growth factor receptor 2-negative and clinically negative axillary lymph nodes. The study plans to enrol 25 patients. Radiotherapy planning will involve the use of CT and MRI in the treatment position. Single-dose PBI of 20 Gy to the tumour and 15 Gy to the surrounding 2 cm of breast tissue will be delivered using a conventional or MR-guided linear accelerator. Tumour response will be monitored preoperatively using MRI and liquid biopsies to identify biomarkers for evaluating radiosensitivity. BCS will be performed 3 (±one) weeks post PBI. The primary endpoint is the incidence of grade 2 or higher treatment-associated acute toxicity within 90 days. Secondary endpoints include the evaluation of acute (grade 1) and late toxicity, radiologic and pathologic response, mastectomy rate, patient-reported outcomes, cosmetic outcome, local, regional and distant recurrence rates, survival outcome and biomarkers in liquid biopsies and tumour tissue. Patients will be followed up to 5 years after PBI.

Ethical approval from the Medical Research Ethics Committee of the Amsterdam UMC has been obtained (NL85983.018.24). The results will be disseminated via peer-reviewed academic journal and presentation at conferences. In addition, summaries will be shared with the participating patients.

The trial was registered prospectively on October 11^th 2024 at clinicaltrials.gov (NCT06640881).

New-onset supraventricular arrhythmia (NOSVA) is the most common arrhythmia in patients with septic shock and is associated with haemodynamic alterations and increased mortality rates. With no data available from randomised trials, clinical practice for patient management varies widely. In this setting, rate control or rhythm control could be beneficial in limiting the duration of shock and preventing evolution to multiorgan dysfunction.

The Control Atrial Fibrillation in Septic shock (CAFS) study is a binational (French and Belgium), multicentre, parallel-group, open-label, randomised controlled superiority trial to compare the efficacy and safety of three management strategies in patients with NOSVA during septic shock. The expected duration of patient enrolment is 42 months, starting from November 2021. Patients will be randomised to receive either risk control (magnesium and control of risk factors for NOSVA), rate control (risk control and low dose of amiodarone) or rhythm control (risk control and cardioversion using high dose of amiodarone with external electrical shock if NOSVA persists) for 7 days. Patients with a history of SVA, NOSVA lasting more than 48 hours, recent cardiac surgery or a contraindication to amiodarone will not be included. We plan to recruit 240 patients. Patients will be randomised on a 1:1:1 basis and stratified by centre. The primary endpoint is a hierarchical criterion at day 28 including all-cause mortality and the duration of septic shock defined as time from randomisation to successful weaning of vasopressors. Secondary outcomes include: individual components of the primary endpoint; arterial lactate clearance at day 3; efficacy at controlling cardiac rhythm at day 7; proportion of patients free from organ dysfunction at day 7; ventricular arrhythmia, conduction disorders, thrombotic events, major bleeding events and acute hepatitis related to amiodarone at day 28; intensive care unit and hospital lengths of stay at day 28.

The study has been approved by the French (Comité Sud-Ouest et Outre-Mer II, France, registration number 2019-A02624-53) and Belgian (Comité éthique de l’hôpital Erasme, Belgium, registration number CCB B4062023000179) ethics committees. Patients will be included after obtaining signed informed consent. The results will be submitted for publication in peer-reviewed journals.

NCT04844801.