Hospital utilisation and the costs associated with complications of ICD implantation in a contemporary primary prevention cohort.

INTRODUCTION: Implantation of an implantable cardioverter defibrillator (ICD) is standard care for primary prevention of sudden cardiac death. However, ICD-related complications are increasing as the population of ICD recipients grows. METHODS: ICD-related complications in a national DO-IT Registry cohort of 1442 primary prevention ICD patients were assessed in terms of additional use of hospital care resources and costs. RESULTS: During a median follow-up of 28.7 months (IQR 25.2-33.7) one or more complications occurred in 13.5% of patients. A complication resulted in a surgical intervention in 53% of cases and required on average 3.65 additional hospital days. The additional hospital costs were €6,876 per complication or €8,110 per patient, to which clinical re-interventions and additional hospital days contributed most. Per category of complications, infections required most hospital utilisation and were most expensive at an average of €22,892. The mean costs were €5,800 for lead-related complications, €2,291 for pocket-related complications and €5,619 for complications due to other causes. We estimate that the total yearly incidence-based costs in the Netherlands for hospital management of ICD-related complications following ICD implantation for primary prevention are €2.7 million. CONCLUSION: Complications following ICD implantation are related to a substantial additional need for hospital resources. When performing cost-effectiveness analyses of ICD implantation, including the costs associated with complications, one should be aware that real-world complication rates may deviate from trial data. Considering the economic implications, strategies to reduce the incidence of complications are encouraged.

Initial experience with AcQMap catheter for treatment of persistent atrial fibrillation and atypical atrial flutter.

INTRODUCTION: The AcQMap High Resolution Imaging and Mapping System was recently introduced. This system provides 3D maps of electrical activation across an ultrasound-acquired atrial surface. METHODS: We evaluated the feasibility and the acute and short-term efficacy and safety of this novel system for ablation of persistent atrial fibrillation (AF) and atypical atrial flutter. RESULTS: A total of 21 consecutive patients (age (mean ± standard deviation) 62 ± 8 years, 23% female) underwent catheter ablation with the use of the AcQMap System. Fourteen patients (67%) were treated for persistent AF and 7 patients (33%) for atypical atrial flutter. Eighteen patients (86%) had undergone at least one prior ablation procedure. Acute success, defined as sinus rhythm without the ability to provoke the clinical arrhythmia, was achieved in 17 patients (81%). At 12 months, 4 patients treated for persistent AF (29%) and 4 patients treated for atypical flutter (57%) remained in sinus rhythm. Complications included hemiparesis, for which intra-arterial thrombolysis was given with subsequent good clinical outcome (n = 1), and complete atrioventricular block, for which a permanent pacemaker was implanted (n = 2). No major complications attributable to the mapping system occurred. CONCLUSION: The AcQMap System is able to provide fast, high-resolution activation maps of persistent AF and atypical atrial flutter. Despite a high acute success rate, the recurrence rate of persistent AF was relatively high. This may be due to the selection of the patients with therapy-resistant arrhythmias and limited experience in the optimal use of this mapping system that is still under development.

Implementing a patient decision aid, a process evaluation of a large-scale pre- and post-implementation trial.

PURPOSE: Patient decision aids (PtDAs) have been reported to have a positive influence on patients making a health care decision in trials. Nevertheless, post-trial implementation is poor. The aim of this study is to explore patient, clinician, and organizational success factors for implementing a PtDA designed for breast cancer patients, facing a decision on their radiation treatment. METHODS: We performed a process evaluation within a multi-center pre- and post-implementation trial. The PtDA was incorporated as much as possible in the logistics of 13 participating centers. Tracking data were collected on PtDA use. Process characteristics were recorded by both clinicians and patients. A logistic regression method was applied to investigate which process characteristics were significantly related to the probability that patients logged in to the PtDA. RESULTS: 189 patients received the PtDA of whom140 (77%) used the PtDA. If patients received the link via the surgery department they were more likely to use the PtDA (OR 9.77 (1.28-74.51)), compared to patients that received the link via the radiation oncology department. If the report of the multidisciplinary team stated that radiation treatment "had to be discussed with the patient", patients were more likely to use the PtDA (OR 2.29 (1.12-4.71)). Educational level was not related to the probability of PtDA use. CONCLUSIONS: We accomplished a high level of PtDA use. Patients were more likely to use the PtDA if they received the link via the surgery department and if "to be discussed with the patient" was written in the multidisciplinary team report.

Changes in anticoagulant prescription in Dutch patients with recent-onset atrial fibrillation: observations from the GARFIELD-AF registry.

BACKGROUND: For the improvement of AF care, it is important to gain insight into current anticoagulation prescription practices and guideline adherence. This report focuses on the largest Dutch subset of AF-patients, derived from the GARFIELD-AF registry. METHODS: Across 35 countries worldwide, patients with newly diagnosed 'non-valvular' atrial fibrillation (AF) with at least one additional risk factor for stroke were included. Dutch patients were enrolled in five, independent, consecutive cohorts from 2010 until 2016. RESULTS: In the Netherlands, 1189 AF-patients were enrolled. The prescription of non-vitamin K antagonist oral anticoagulants (NOAC) has increased sharply, and as per 2016, more patients were initiated on NOACs instead of vitamin K antagonists (VKA). In patients with a class I recommendation for anticoagulation, only 7.5% compared to 30.0% globally received no anticoagulation. Reasons for withholding anticoagulation in these patients were unfortunately often unclear. CONCLUSIONS: The data from the GARFIELD-AF registry shows the rapidly changing anticoagulation preference of Dutch physicians in newly diagnosed AF. Adherence to European AF guidelines in terms of anticoagulant regimen would appear to be appropriate. In absence of structured follow up of AF patients on NOAC, the impact of these rapid practice changes in anticoagulation prescription in the Netherlands remains to be established.

Elicitation of preferences in the second half of the shared decision making process needs attention; a qualitative study.

BACKGROUND: It is known that the use of a Patient Decision Aid (PtDA), combined with advice for professionals on how and when to use it, can enhance the involvement of patients in the treatment decision. However, we need more knowledge with respect to the intention-behaviour gap. This study aims to analyse patients' experiences with the Shared Decision Making (SDM) process to find clues to close this gap. METHODS: This qualitative study was part of a pilot study aiming to implement SDM in early adopter breast cancer teams. Patients were given access to a personalised PtDA. Breast cancer teams were instructed on how and when to deliver the PtDA. We interviewed 20 patients about their experience with the PtDA and SDM in general. RESULTS: Most patients experienced SDM, though to a certain extent. Choice talk and option talk were commonly experienced, however the elicitation of preferences and decision talk was rare. The PtDA was used by the majority of patients (N = 13), all indicating that it was useful, especially to recall all the information given. Patients appreciated the contribution of breast cancer nurses in the SDM process. They considered them as true case managers, easy to approach and supportive. CONCLUSION: Although patients felt well-informed and satisfied about risk-communication, the elicitation of preferences appeared very limited to non-existent. We recommend that breast cancer teams divide tasks in the SDM process and reallocate the elicitation of preferences to the nurses in a well-defined clinical pathway.

Therapeutic options for patients with advanced atrial fibrillation: from lifestyle and medication to catheter and surgical ablation.

Atrial fibrillation (AF) is part of a vicious cycle that includes multiple cardiovascular risk factors and comorbidity which can promote atrial remodelling and AF progression. Most AF-related risk factors-hypertension, diabetes, sleep apnoea, obesity and sedentary lifestyle-are in essence modifiable which may prevent AF development. Treatment of associated cardiovascular conditions may prevent both symptoms and future cardiovascular events. For advanced forms of symptomatic AF refractory to lifestyle management and optimal medication, invasive ablation therapies have become a cornerstone. Although electrical trigger isolation from the pulmonary veins is reasonably effective and safe, more potent energy sources including high output-short duration radiofrequency, ultra-low cryo-energy, and electroporation, as well as more sophisticated arrays, balloons, and lattice-tipped catheter tools, are on their way to eliminate existing pitfalls and simplify the procedure. Electroanatomical navigation and mapping systems are becoming available to provide real-time information on ablation lesion quality and the critical pathways of AF in the individual patient to guide more extensive ablation strategies that may enhance long-term outcome for freedom of advanced AF. Surgical techniques, either stand-alone or concomitant to structural cardiac repair, hybrid, or convergent, with novel less invasive access options are developing and can be helpful in situations unsuitable for catheter ablation.

Risk of Positive Sentinel Lymph Node After Neoadjuvant Systemic Therapy in Clinically Node-Negative Breast Cancer: Implications for Postmastectomy Radiation Therapy and Immediate Breast Reconstruction.

BACKGROUND: Residual axillary lymph node involvement after neoadjuvant systemic therapy (NST) is the determining factor for postmastectomy radiation therapy (PMRT). Preoperative identification of patients needing PMRT is essential to enable shared decision-making when choosing the optimal timing of breast reconstruction. We determined the risk of positive sentinel lymph node (SLN) after NST in clinically node-negative (cN0) breast cancer. METHODS: All cT1-3N0 patients treated with NST followed by mastectomy and SLNB between 2010 and 2016 were identified from the Netherlands Cancer Registry. Rate of positive SLN for different breast cancer subtypes was determined. Logistic regression analysis was performed to determine correlated clinicopathological variables with positive SLN. RESULTS: In total 788 patients were included, of whom 25.0% (197/788) had positive SLN. cT1-3N0 ER+HER2+, cT1-3N0 ER-HER2+ , and cT1-2N0 triple-negative patients had the lowest rate of positive SLN: 7.2-11.5%, 0-6.3%, and 2.9-6.2%, respectively. cT1-3N0 ER+HER2- and cT3N0 triple-negative patients had the highest rate of positive SLN: 23.8-41.7% and 30.4%, respectively. Multivariable regression analysis showed that cT2 (odds ratio [OR] 1.93; 95% confidence interval [CI] 1.01-3.96), cT3 (OR 2.56; 95% CI 1.30-5.38), grade 3 (OR 0.44; 95% CI 0.21-0.91), and ER+HER2- subtype (OR 3.94; 95% CI 1.77-8.74) were correlated with positive SLN. CONCLUSIONS: In cT1-3N0 ER+HER2+, cT1-3N0 ER-HER2+, and cT1-2N0 triple-negative patients treated with NST, immediate reconstruction can be considered an acceptable option due to low risk of positive SLN. In cT1-3N0 ER+HER2- and cT3N0 triple-negative patients treated with NST, risks and benefits of immediate reconstruction should be discussed with patients due to the relatively high risk of positive SLN.

Left atrial appendage closure in atrial fibrillation patients with prior major bleeding or ineligible for oral anticoagulation.

AIMS: Oral anticoagulation (OAC) reduces the ischaemic stroke risk in patients with atrial fibrillation (AF), but in turn leads to an increased risk of adverse bleeding events. Alternatively, left atrial appendage closure (LAAC) using a mechanical device might overcome these bleeding complications. However, evidence regarding LAAC in patients at high bleeding risk is scarce. This study evaluates the clinical features of AF patients with previous bleeding that underwent LAAC. METHODS: In this retrospective cohort study patients with previous major bleeding or a bleeding predisposition scheduled for transcatheter LAAC were included. The frequency and type of previous bleeding events and prevalence of bleeding and ischaemic stroke during follow-up were evaluated. RESULTS: A total of 73 patients (58% male, age 72.1 ± 7.2 years; CHA2DS2-VASc 4.5 [3.0-5.0]; HAS-BLED 4.0 [3.0-4.0]; 46% paroxysmal AF) were included. Previous bleeding occurred from intracranial (n = 50, 69%), gastro-intestinal (n = 13, 18%) or multiple (n = 16, 22%) foci. After OAC discontinuation due to bleeding, 19% suffered subsequent stroke. LAAC was successful in 96% of patients. During a median of almost 3 years' follow-up recurrent major bleeding occurred in 4 patients (5.5%) despite OAC discontinuation in 93.2%. A total of 6 ischaemic strokes were observed, resulting in an annualised stroke rate of 2.9% compared to a calculated expected stroke rate of 6.7%. CONCLUSIONS: Percutaneous LAAC may provide an alternative strategy to long-term OAC therapy in AF patients with a high bleeding risk. During follow-up, both ischaemic stroke and recurrent bleeding rates were lower than expected based on the CHA2DS2-VASc and HAS-BLED scores respectively.

Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: An individual patient data meta-analysis of 22 RCTs.

OBJECTIVE: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. METHODS: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables. RESULTS: PSI significantly improved QoL (ß = 0.14,95%CI = 0.06;0.21), EF (ß = 0.13,95%CI = 0.05;0.20), and SF (ß = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. CONCLUSIONS: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.

Silent atrial fibrillation in patients with an implantable cardioverter defibrillator and coronary artery disease (INDICO AF) trial: study rationale and design.

BACKGROUND: Timely detection of atrial fibrillation (AF) in implantable cardioverter defibrillator (ICD) patients is clinically important for prevention of AF-related complications and inappropriate shocks. Patients with coronary artery disease (CAD) and a dual or triple chamber ICD show a high incidence of device-detected AF. Whether CAD patients with a single chamber ICD carry a similar risk for device-detected AF remains unknown. STUDY DESIGN: The INDICO AF trial is an investigator-initiated, multicentre, observational study evaluating the incidence of subclinical AF (SCAF) in CAD patients who will receive a single chamber ICD as primary prevention for sudden cardiac death (SCD). Fifty patients will receive a single chamber ICD with an integrated RR interval based AF detection algorithm. In combination with remote monitoring, rhythm data will be collected monthly. The primary endpoint is the incidence of SCAF at 1 year of follow-up; secondary endpoints include time until 10 and 20% of the patients have a first episode of SCAF. All patients in whom SCAF is detected will be invited for an outpatient visit and will receive adequate anticoagulation treatment when appropriate according to the CHA2DS2-VASc score and current guidelines. CONCLUSION: The INDICO AF trial will quantify the incidence of SCAF in patients with an ICD and CAD. The study will underscore the clinical value of SCAF detection in single chamber ICD patients using remote patient monitoring and may improve patient care. This trial is registered at trialregister.nl with trial NTR6910.

Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a Dutch randomized controlled multicentre trial (BOOG 2013-08).

BACKGROUND: Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013-08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy. METHODS: The BOOG 2013-08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1-2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up. DISCUSSION: If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival. TRIAL REGISTRATION: The BOOG 2013-08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. https://clinicaltrials.gov/ct2/show/NCT02271828.

Developing a patient decision aid for the treatment of women with early stage breast cancer: the struggle between simplicity and complexity.

BACKGROUND: A patient decision aid (PtDA) can support shared decision making (SDM) in preference-sensitive care, with more than one clinically applicable treatment option. The development of a PtDA is a complex process, involving several steps, such as designing, developing and testing the draft with all the stakeholders, known as alpha testing. This is followed by testing in 'real life' situations, known as beta testing, and then finalising the definite version. Our aim was developing and alpha testing a PtDA for primary treatment of early stage breast cancer, ensuring that the tool is considered relevant, valid and feasible by patients and professionals. METHODS: Our qualitative descriptive study applied various methods including face-to-face think-aloud interviews, a focus group and semi-structured telephone interviews. The study population consisted of breast cancer patients facing the choice between breast-conserving therapy with or without preceding neo-adjuvant chemotherapy and mastectomy, and professionals involved in breast cancer care in dedicated multidisciplinary breast cancer teams. RESULTS: A PtDA was developed in four iterative test rounds, taking nearly 2 years, involving 26 patients and 26 professionals. While the research group initially opted for simplicity for the sake of implementation, the clinicians objected that the complexity of the decision could not be ignored. Other topics of concern were the conflicting views of professionals and patients regarding side effects, the amount of information and how to present it. CONCLUSION: The development was an extensive process, because the professionals rejected the simplifications proposed by the research group. This resulted in the development of a completely new draft PtDA, which took double the expected time and resources. The final version of the PtDA appeared to be well-appreciated by professionals and patients, although its acceptability will only be proven in actual practice (beta testing). TRIAL REGISTRATION: NTR TC 5721 .

Outpatient treatment with the wearable cardioverter defibrillator: clinical experience in two Dutch centres.

INTRODUCTION: The latest European Society of Cardiology Guidelines recommend consideration of a wearable cardioverter-defibrillator (WCD) for patients with a poor left ventricular ejection fraction (LVEF) who are at risk of sudden arrhythmic death but are not eligible for an implantable defibrillator. For these patients a WCD can be an alternative to long-term hospitalisation. PURPOSE: To evaluate the use of WCD therapy in these patient groups in two Dutch centres. METHODS: All consecutive patients treated with the WCD between 2009 and 2016 were included from two centres in the Netherlands. Data on events and compliance were collected retrospectively through home monitoring systems and adjudicated by the investigators. RESULTS: A total of 79 patients were treated with a WCD. Common indications were newly diagnosed cardiomyopathy without optimal medical treatment in 46 patients (58.2%) and bridge to implantable cardioverter-defibrillator (ICD) implant in 33 patients (41.8%). Bridge to implant indications consisted of contraindications for immediate implantation such as infections (e. g. previous device-related infections) and radiotherapy. Compliance was over 97% per day (median 23.3 h, 22.6-23.7), during a median of 79 days (50.0-109.8.0). Two patients (2.6%) received an appropriate shock (annual rate 13.6%), there was 1 (1.3%) inappropriate shock (annual rate 6.7%). In 24 patients (52.2%) without optimal medical treatment, the LVEF was sufficiently improved and ICD implant was avoided. Eight (10.1%) patients did not receive an ICD. In 45 patients an ICD was implanted (57.0%). CONCLUSION: WCD therapy provides a safe and effective treatment in outpatient setting for patients at high risk for sudden cardiac death and reduces the number of ICDs implanted.

Feasibility of multiplane microtransoesophageal echocardiographic guidance in structural heart disease transcatheter interventions in adults.

INTRODUCTION: Structural heart interventions are guided by transoesophageal or intracardiac echocardiography (TEE/ICE). MicroTEE, developed for paediatric purposes, is smaller and therefore less invasive and traumatic, avoiding the need for general anaesthesia. We aimed to show feasibility of procedural guidance by comparing image quality of microTEE with standard TEE and ICE during adult transcatheter interventions, and assess the accuracy in obtaining left atrial appendage (LAA) measurements between the microTEE probe and standard TEE. METHODS AND RESULTS: We prospectively included 49 patients (20 women, 64 ± 18 years). Intraprocedural images were obtained by using the microTEE probe and standard (2D and 3D) TEE (LAA closure, MitraClip implantation) or ICE (interatrial communication closure, transseptal puncture for left atrial ablation). Two echocardiographers independently assessed image quality from 1 (excellent) to 4 (poor) and performed LAA measurements. Use of microTEE was not related to significant discomfort. Image quality obtained with the microTEE probe was lower than with standard TEE (2 [1-2] vs. 1 [1-2]; p = 0.04) and comparable with ICE images (2 [1-2] vs. 2 [1-2], p = 0.13). MicroTEE showed a wider field of view than ICE. LAA measurements on images obtained by microTEE were strongly associated with standard TEE. CONCLUSIONS: MicroTEE seems feasible for guidance during transcatheter heart interventions in adults. MicroTEE imaging offers a wider field of view than ICE, and its accuracy is comparable with TEE. In transcatheter interventions performed under conscious sedation, microTEE might be a viable and advantageous alternative to standard TEE or ICE.

Dutch outcome in implantable cardioverter-defibrillator therapy (DO-IT): registry design and baseline characteristics of a prospective observational cohort study to predict appropriate indication for implantable cardioverter-defibrillator.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are widely used for the prevention of sudden cardiac death. At present, both clinical benefit and cost-effectiveness of ICD therapy in primary prevention patients are topics of discussion, as only a minority of these patients will eventually receive appropriate ICD therapy. METHODS/DESIGN: The DO-IT Registry is a nationwide prospective cohort with a target enrolment of 1,500 primary prevention ICD patients with reduced left ventricular function in a setting of structural heart disease. The primary outcome measures are death and appropriate ICD therapy for ventricular tachyarrhythmias. Secondary outcome measures are inappropriate ICD therapy, death of any cause, hospitalisation for ICD related complications and for cardiovascular reasons. As of December 2016, data on demographic, clinical, and ICD characteristics of 1,468 patients have been collected. Follow-up will continue up to 24 months after inclusion of the last patient. During follow-up, clinical and ICD data are collected based on the normal follow-up of these patients, assuming ICD interrogations take place every six months and clinical follow-up is once a year. At baseline, the mean age was 66 (standard deviation [SD] 10) years and 27% were women. CONCLUSION: The DO-IT Registry represents a real-world nationwide cohort of patients receiving ICDs for primary prevention of sudden cardiac death with reduced left ventricular function in a setting of structural heart disease. The registry investigates the efficacy of the current practice and aims to develop prediction rules to identify subgroups who will not (sufficiently) benefit from ICD implantation and to provide results regarding costs and budget impact of targeted supply of primary preventions ICDs.

The value of completion axillary treatment in sentinel node positive breast cancer patients undergoing a mastectomy: a Dutch randomized controlled multicentre trial (BOOG 2013-07).

BACKGROUND: Trials failed to demonstrate additional value of completion axillary lymph node dissection in case of limited sentinel lymph node metastases in breast cancer patients undergoing breast conserving therapy. It has been suggested that the low regional recurrence rates in these trials might partially be ascribed to accidental irradiation of part of the axilla by whole breast radiation therapy, which precludes extrapolation of results to mastectomy patients. The aim of the randomized controlled BOOG 2013-07 trial is therefore to investigate whether completion axillary treatment can be safely omitted in sentinel lymph node positive breast cancer patients treated with mastectomy. DESIGN: This study is designed as a non-inferiority randomized controlled multicentre trial. Women aged 18 years or older diagnosed with unilateral invasive clinically T1-2 N0 breast cancer who are treated with mastectomy, and who have a maximum of three axillary sentinel lymph nodes containing micro- and/or macrometastases, will be randomized for completion axillary treatment versus no completion axillary treatment. Completion axillary treatment can consist of completion axillary lymph node dissection or axillary radiation therapy. Primary endpoint is regional recurrence rate at 5 years. Based on a 5-year regional recurrence free survival rate of 98 % among controls and 96 % for study subjects, the sample size amounts 439 per arm (including 10 % lost to follow-up), to be able to reject the null hypothesis that the rate for study and control subjects is inferior by at least 5 % with a probability of 0.8. Results will be reported after 5 and 10 years of follow-up. DISCUSSION: We hypothesize that completion axillary treatment can be safely omitted in sentinel node positive breast cancer patients undergoing mastectomy. If confirmed, this study will significantly decrease the number of breast cancer patients receiving extensive treatment of the axilla, thereby diminishing the risk of morbidity and improving quality of life, while maintaining excellent regional control and without affecting survival. TRIAL REGISTRATION: The BOOG 2013-07 study is registered in the register of ClinicalTrials.gov since April 10, 2014, Identifier: NCT02112682 .

External validation of a lung cancer-based prediction model for two-year mortality in esophageal cancer patient cohorts.

PURPOSE/OBJECTIVE: Chemo-radiotherapy can improve the oncological outcome of esophageal cancer (EC) patients, but may cause long term radiation-induced toxicity, including an increased risk of non-cancer related death. For lung cancer patients, a model to predict 2-year total mortality using mean heart dose (MHD) and gross tumor volume (GTV) has previously been developed and validated. This project aimed to externally validate this model in EC patients. METHODS: Five EC patient cohorts from 3 different Dutch centres were used for model validation. External validity of the model was assessed separately in definitive (n = 170) and neo-adjuvant (n = 568) chemoradiotherapy (dCRT and nCRT) patients. External validity was assessed in terms of calibration by calibration plots, calibration-in-the-large (CITL) and calibration slope (CS), and discrimination by assessment of the c-statistic. If suboptimal model performance was observed, the model was further updated accordingly. RESULTS: For the dCRT patients, good calibration was found after adjustment of the intercept (CITL 0.00; CS 1.08). The c-statistic of the adjusted model was 0.67 (95%CI: 0.58 to 0.75). For nCRT patients the model needed adjustment of both the slope and the intercept because of initial miscalibration in the validation population (CITL 0.00; CS 1.72). After recalibration, the model showed perfect calibration (i.e., CITL 0, CS 1), as is common after recalibration. The c-statistic of the recalibrated model equaled 0.62 (95%CI: 0.57 to 0.67). CONCLUSION: The existing model for 2-year mortality prediction in lung cancer patients, based on the predictive factors MHD and GTV, showed good performance in EC patients after updating the intercept and/or slope of the original model.

The Assisi think tank focus review on postoperative radiation for lobular breast cancer.

The "Assisi Think Tank Meeting" (ATTM) on Breast Cancer, endorsed by the European Society for Radiotherapy & Oncology (ESTRO) and the Italian Association of Radiotherapy and Clinical Oncology (AIRO), and conducted under the auspices of the European Society of Breast Cancer Specialists (EUSOMA), is a bi-annual meeting aiming to identify major clinical challenges in breast cancer radiation therapy (RT) and proposing clinical trials to address them. The topics discussed at the meeting are pre-selected by the steering committee. At the meeting, these topics are discussed in different working groups (WG), after preparation of the meeting by performing a systematic review of existing data and of ongoing trials. Prior to the meeting, each WG designs a survey on the topic to be discussed to reflect current clinical practice and to identify areas requiring further research. Herein, we present the work done by the Assisi WG focusing on lobular carcinoma and the RT perspectives in its treatment, including providing recommendations for locoregional therapy, mainly RT for patients with non-metastatic lobular breast cancer.

Quality assurance of radiation therapy after breast-conserving surgery among patients in the BOOG 2013-08 trial.

BACKGROUND AND PURPOSE: In the BOOG 2013-08 trial (NCT02271828), cT1-2N0 breast cancer patients were randomized between breast conserving surgery with or without sentinel lymph node biopsy (SLNB) followed by whole breast radiotherapy (WBRT). While awaiting primary endpoint results (axillary recurrence rate), this study aims to perform a quality assurance analysis on protocol adherence and (incidental) axillary radiation therapy (RT) dose. MATERIALS AND METHODS: Patients were enrolled between 2015 and 2022. Data on prescribed RT and (in 25% of included patients) planning target volumes (PTV) parameters were recorded for axillary levels I-IV and compared between treatment arms. Multivariable linear regression analysis was performed to determine prognostic variables for incidental axillary RT dose. RESULTS: 1,439/1,461 included patients (98.5%) were treated according to protocol and 87 patients (5.9%) received regional RT (SLNB 10.9%, no-SLNB 1.5 %). In 326 patients included in the subgroup analysis, the mean incidental PTV dose at axilla level I was 59.5% of the prescribed breast RT dose. In 5 patients (1.5%) the mean PTV dose at level I was ≥95% of the prescribed breast dose. No statistically or clinically significant differences regarding incidental axillary RT dose were found between treatment arms. Tumour bed boost (yes/no) was associated with a higher incidental mean dose in level I (R2 = 0.035, F(6, 263) = 1.532, p 0.168). CONCLUSION: The results indicate that RT-protocol adherence was high, and that incidental axillary RT dose was low in the BOOG 2013-08 trial. Potential differences between treatmentarms regarding the primary endpoint can thus not be attributed to different axillary radiation doses.

Percutaneous left atrial appendage occlusion in patients with a cardiac implantable electronic device.

BACKGROUND: Left atrial appendage occlusion (LAAO) may be a viable option for stroke prevention in patients with non-valvular atrial fibrillation and a contraindication for oral anticoagulation. No evidence evaluating the safety of this procedure in patients with a cardiac implantable electronic device (CIED) exists. The aim of this study was to evaluate whether CIED function is affected by LAAO and to explore LAAO procedural characteristics and complications in patients with a CIED. METHODS: This single-center cohort study included consecutive patients scheduled for percutaneous LAAO. Patients with a CIED prior to LAAO were selected and compared to the patients without CIED, concerning procedural characteristics and peri-procedural complications. In the group of patients with CIEDs, essential pacemaker integrity parameters were compared before and after the procedure to detect possible micro and macro lead displacements. RESULTS: Thirty-one patients with CIED were scheduled for LAAO (age 73.7 ± 5.4 years, 65% males, CHA2DS2-VASc 4.3 ± 1.5, and HAS-BLED 3.3 ± 1.0). The 245 patients without CIED were younger, and HAS-BLED-score was slightly lower (69.4 ± 8.2 years, p < 0.001; 2.8 ± 1.0, p = 0.022). Patients without CIED more frequently underwent LAAO combined with catheter ablation (p = 0.002). All other procedural characteristics were comparable between both groups. No visible lead displacement was observed on chest X-ray after LAAO. Additionally, no differences in impedance, threshold, or intracardiac sensing in various CIED lead locations were found prior versus post LAAO. CONCLUSION: This study supports the feasibility and safety of LAAO in patients with a CIED.