Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases.

BACKGROUND: Trials evaluating the omission of completion axillary-lymph-node dissection in patients with clinically node-negative breast cancer and sentinel-lymph-node metastases have been compromised by limited statistical power, uncertain nodal radiotherapy target volumes, and a scarcity of data on relevant clinical subgroups. METHODS: We conducted a noninferiority trial in which patients with clinically node-negative primary T1 to T3 breast cancer (tumor size, T1, ≤20 mm; T2, 21 to 50 mm; and T3, >50 mm in the largest dimension) with one or two sentinel-node macrometastases (metastasis size, >2 mm in the largest dimension) were randomly assigned in a 1:1 ratio to completion axillary-lymph-node dissection or its omission (sentinel-node biopsy only). Adjuvant treatment and radiation therapy were used in accordance with national guidelines. The primary end point was overall survival. We report here the per-protocol and modified intention-to-treat analyses of the prespecified secondary end point of recurrence-free survival. To show noninferiority of sentinel-node biopsy only, the upper boundary of the confidence interval for the hazard ratio for recurrence or death had to be below 1.44. RESULTS: Between January 2015 and December 2021, a total of 2766 patients were enrolled across five countries. The per-protocol population included 2540 patients, of whom 1335 were assigned to undergo sentinel-node biopsy only and 1205 to undergo completion axillary-lymph-node dissection (dissection group). Radiation therapy including nodal target volumes was administered to 1192 of 1326 patients (89.9%) in the sentinel-node biopsy-only group and to 1058 of 1197 (88.4%) in the dissection group. The median follow-up was 46.8 months (range, 1.5 to 94.5). Overall, 191 patients had recurrence or died. The estimated 5-year recurrence-free survival was 89.7% (95% confidence interval [CI], 87.5 to 91.9) in the sentinel-node biopsy-only group and 88.7% (95% CI, 86.3 to 91.1) in the dissection group, with a country-adjusted hazard ratio for recurrence or death of 0.89 (95% CI, 0.66 to 1.19), which was significantly (P<0.001) below the prespecified noninferiority margin. CONCLUSIONS: The omission of completion axillary-lymph-node dissection was noninferior to the more extensive surgery in patients with clinically node-negative breast cancer who had sentinel-node macrometastases, most of whom received nodal radiation therapy. (Funded by the Swedish Research Council and others; SENOMAC ClinicalTrials.gov number, NCT02240472.).

Transcatheter or surgical aortic valve implantation: 10-year outcomes of the NOTION trial.

BACKGROUND AND AIMS: Transcatheter aortic valve implantation (TAVI) has become a viable treatment option for patients with severe aortic valve stenosis across a broad range of surgical risk. The Nordic Aortic Valve Intervention (NOTION) trial was the first to randomize patients at lower surgical risk to TAVI or surgical aortic valve replacement (SAVR). The aim of the present study was to report clinical and bioprosthesis outcomes after 10 years. METHODS: The NOTION trial randomized 280 patients to TAVI with the self-expanding CoreValve (Medtronic Inc.) bioprosthesis (n = 145) or SAVR with a bioprosthesis (n = 135). The primary composite outcome was the risk of all-cause mortality, stroke, or myocardial infarction. Bioprosthetic valve dysfunction (BVD) was classified as structural valve deterioration (SVD), non-structural valve dysfunction (NSVD), clinical valve thrombosis, or endocarditis according to Valve Academic Research Consortium-3 criteria. Severe SVD was defined as (i) a transprosthetic gradient of 30 mmHg or more and an increase in transprosthetic gradient of 20 mmHg or more or (ii) severe new intraprosthetic regurgitation. Bioprosthetic valve failure (BVF) was defined as the composite rate of death from a valve-related cause or an unexplained death following the diagnosis of BVD, aortic valve re-intervention, or severe SVD. RESULTS: Baseline characteristics were similar between TAVI and SAVR: age 79.2 ± 4.9 years and 79.0 ± 4.7 years (P = .7), male 52.6% and 53.8% (P = .8), and Society of Thoracic Surgeons score < 4% of 83.4% and 80.0% (P = .5), respectively. After 10 years, the risk of the composite outcome all-cause mortality, stroke, or myocardial infarction was 65.5% after TAVI and 65.5% after SAVR [hazard ratio (HR) 1.0; 95% confidence interval (CI) 0.7-1.3; P = .9], with no difference for each individual outcome. Severe SVD had occurred in 1.5% and 10.0% (HR 0.2; 95% CI 0.04-0.7; P = .02) after TAVI and SAVR, respectively. The cumulative incidence for severe NSVD was 20.5% and 43.0% (P < .001) and for endocarditis 7.2% and 7.4% (P = 1.0) after TAVI and SAVR, respectively. No patients had clinical valve thrombosis. Bioprosthetic valve failure occurred in 9.7% of TAVI and 13.8% of SAVR patients (HR 0.7; 95% CI 0.4-1.5; P = .4). CONCLUSIONS: In patients with severe AS and lower surgical risk randomized to TAVI or SAVR, the risk of major clinical outcomes was not different 10 years after treatment. The risk of severe bioprosthesis SVD was lower after TAVR compared with SAVR, while the risk of BVF was similar.

Randomized comparison of TAVI valves: The Compare-TAVI trial.

INTRODUCTION: Based on technical advancements and clinical evidence, transcatheter aortic valve implantation (TAVI) has been widely adopted. New generation TAVI valve platforms are continually being developed. Ideally, new valves should be superior or at least non-inferior regarding efficacy and safety, when compared to best-in-practice contemporary TAVI valves. METHODS AND ANALYSIS: The Compare-TAVI trial (ClinicalTrials.gov NCT04443023) was launched in 2020, to perform a 1:1 randomized comparison of new vs contemporary TAVI valves, preferably in all comers. Consecutive cohorts will be launched with sample sizes depending on the choice of interim analyses, expected event rates, and chosen superiority or non-inferiority margins. Enrollment has just been finalized in cohort B, comparing the Sapien 3/Sapien 3 Ultra Transcatheter Heart Valve (THV) series (Edwards Lifesciences, Irvine, California, USA) and the Myval/Myval Octacor THV series (Meril Life Sciences Pvt. Ltd., Vapi, Gujarat, India) balloon expandable valves. This non-inferiority study was aimed to include 1062 patients. The 1-year composite safety and efficacy endpoint comprises death, stroke, moderate-severe aortic regurgitation, and moderate-severe valve deterioration. Patients will be followed until withdrawal of consent, death, or completion of 10-year follow-up, whichever comes first. Secondary endpoints will be monitored at 30 days, 1, 3, 5, and 10 years. SUMMARY: The Compare-TAVI organization will launch consecutive cohorts wherein patients scheduled for TAVI are randomized to one of two valves. The aim is to ensure that the short- and long-term performance and safety of new valves being introduced is benchmarked against what achieved by best-in-practice contemporary valves.

Geometric distortions in clinical MRI sequences for radiotherapy: insights gained from a multicenter investigation.

BACKGROUND: As magnetic resonance imaging (MRI) becomes increasingly integrated into radiotherapy (RT) for enhanced treatment planning and adaptation, the inherent geometric distortion in acquired MR images pose a potential challenge to treatment accuracy. This study aimed to evaluate the geometric distortion levels in the clinical MRI protocols used across Danish RT centers and discuss influence of specific sequence parameters. Based on the variety in geometric performance across centers, we assess if harmonization of MRI sequences is a relevant measure. MATERIALS AND METHODS: Nine centers participated with 12 MRI scanners and MRI-Linacs (MRL). Using a travelling phantom approach, a reference MRI sequence was used to assess variation in baseline distortion level between scanners. The phantom was also scanned with local clinical MRI sequences for brain, head/neck (H/N), abdomen, and pelvis. The influence of echo time, receiver bandwidth, image weighting, and 2D/3D acquisition was investigated. RESULTS: We found a large variation in geometric accuracy across 93 clinical sequences examined, exceeding the baseline variation found between MRI scanners (σ = 0.22 mm), except for abdominal sequences where the variation was lower. Brain and abdominal sequences showed lowest distortion levels ([0.22, 2.26] mm), and a large variation in performance was found for H/N and pelvic sequences ([0.19, 4.07] mm). Post hoc analyses revealed that distortion levels decreased with increasing bandwidth and a less clear increase in distortion levels with increasing echo time. 3D MRI sequences had lower distortion levels than 2D (median of 1.10 and 2.10 mm, respectively), and in DWI sequences, the echo-planar imaging read-out resulted in highest distortion levels. CONCLUSION: There is a large variation in the geometric distortion levels of clinical MRI sequences across Danish RT centers, and between anatomical sites. The large variation observed makes harmonization of MRI sequences across institutions and adoption of practices from well-performing anatomical sites, a relevant measure within RT.

Patient-reported lower limb edema after primary radiotherapy for prostate cancer.

BACKGROUND: Secondary lymphedema is a known side effect to radiotherapy (RT), but limited information regarding prevalence and risk factors for lower limb edema (LLE) after curative radiotherapy in patients with prostate cancer (PCa) is available. This study provides a descriptive analysis of patient-reported LLE with analysis of risk factors in a cohort of patients with PCa treated with curative RT. MATERIAL AND METHODS: A total of 302 patients with PCa with prospective registration of patient-reported LLE (EORTC QLQ-PR25 (Question 46)) were included. Analysis of LLE was done with the calculation of prevalence rates and Kaplan-Meier statistics. Risk factors for LLE were analyzed multivariate with Cox regression analysis. RESULTS: At a median follow-up of 15 (3-51) months, the overall crude incidence of patients reporting 'quite a bit' or 'a lot' of LLE was 49 (16.2%) and 21 (7.0%), respectively. The baseline prevalence rate of 'quite a bit' and 'a lot' of LLE was 5.0% and 0.8%, respectively. During follow-up the prevalence rate for 'quite a bit' or 'a lot' of LLE increased significantly and remained constant from 6 months where 11.5% (±1.7%) reported 'quite a bit' and 2.9% (±0.5%) reported 'very much' LLE (p < 0.001), respectively.Significant risk factors (p < 0.10) for LLE in univariate analysis included lymph node irradiation (HR:2.325), baseline Body Mass Index (BMI) (HR:1.100), Charlson Comorbidity Index (HR:1.227), Androgen Deprivation Therapy (HR:2,979), and Performance Status (HR:0.594). Only high BMI (HR:1.091) remained significant in multivariate analysis with a three-fold increase in LLE in patients with BMI ≥ 30 compared to normal weight patients. CONCLUSION: Severe patient-reported LLE after curative RT for PCa is rare. Significantly more patients with a high BMI report 'quite a bit' or 'very much' LLE compared to patients with a normal BMI. Obese PCa patients could be offered a rehabilitation program for early detection and management of LLE.

A national repository of complete radiotherapy plans: design, Results, and experiences.

BACKGROUND: Previously, many radiotherapy (RT) trials were based on a few selected dose measures. Many research questions, however, rely on access to the complete dose information. To support such access, a national RT plan database was created. The system focuses on data security, ease of use, and re-use of data. This article reports on the development and structure, and the functionality and experience of this national database. METHODS AND MATERIALS: A system based on the DICOM-RT standard, DcmCollab, was implemented with direct connections to all Danish RT centres. Data is segregated into any number of collaboration projects. User access to the system is provided through a web interface. The database has a finely defined access permission model to support legal requirements. RESULTS: Currently, data for more than 14,000 patients have been submitted to the system, and more than 50 research projects are registered. The system is used for data collection, trial quality assurance, and audit data set generation.Users reported that the process of submitting data, waiting for it to be processed, and then manually attaching it to a project was resource intensive. This was accommodated with the introduction of triggering features, eliminating much of the need for users to manage data manually. Many other features, including structure name mapping, RT plan viewer, and the Audit Tool were developed based on user input. CONCLUSION: The DcmCollab system has provided an efficient means to collect and access complete datasets for multi-centre RT research. This stands in contrast with previous methods of collecting RT data in multi-centre settings, where only singular data points were manually reported. To accommodate the evolving legal environment, DcmCollab has been defined as a 'data processor', meaning that it is a tool for other research projects to use rather than a research project in and of itself.

Eight-year outcomes for patients with aortic valve stenosis at low surgical risk randomized to transcatheter vs. surgical aortic valve replacement.

AIMS: The aims of the study were to compare clinical outcomes and valve durability after 8 years of follow-up in patients with symptomatic severe aortic valve stenosis at low surgical risk treated with either transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR). METHODS AND RESULTS: In the NOTION trial, patients with symptomatic severe aortic valve stenosis were randomized to TAVI or SAVR. Clinical status, echocardiography, structural valve deterioration, and failure were assessed using standardized definitions. In total, 280 patients were randomized to TAVI (n = 145) or SAVR (n = 135). Baseline characteristics were similar, including mean age of 79.1 ± 4.8 years and a mean STS score of 3.0 ± 1.7%. At 8-year follow-up, the estimated risk of the composite outcome of all-cause mortality, stroke, or myocardial infarction was 54.5% after TAVI and 54.8% after SAVR (P = 0.94). The estimated risks for all-cause mortality (51.8% vs. 52.6%; P = 0.90), stroke (8.3% vs. 9.1%; P = 0.90), or myocardial infarction (6.2% vs. 3.8%; P = 0.33) were similar after TAVI and SAVR. The risk of structural valve deterioration was lower after TAVI than after SAVR (13.9% vs. 28.3%; P = 0.0017), whereas the risk of bioprosthetic valve failure was similar (8.7% vs. 10.5%; P = 0.61). CONCLUSIONS: In patients with severe aortic valve stenosis at low surgical risk randomized to TAVI or SAVR, there were no significant differences in the risk for all-cause mortality, stroke, or myocardial infarction, as well as the risk of bioprosthetic valve failure after 8 years of follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01057173.

Long-term outcomes after transcatheter aortic valve implantation in failed bioprosthetic valves.

AIMS: Due to bioprosthetic valve degeneration, aortic valve-in-valve (ViV) procedures are increasingly performed. There are no data on long-term outcomes after aortic ViV. Our aim was to perform a large-scale assessment of long-term survival and reintervention after aortic ViV. METHODS AND RESULTS: A total of 1006 aortic ViV procedures performed more than 5 years ago [mean age 77.7 ± 9.7 years; 58.8% male; median STS-PROM score 7.3% (4.2-12.0)] were included in the analysis. Patients were treated with Medtronic self-expandable valves (CoreValve/Evolut, Medtronic Inc., Minneapolis, MN, USA) (n = 523, 52.0%), Edwards balloon-expandable valves (EBEV, SAPIEN/SAPIEN XT/SAPIEN 3, Edwards Lifesciences, Irvine, CA, USA) (n = 435, 43.2%), and other devices (n = 48, 4.8%). Survival was lower at 8 years in patients with small-failed bioprostheses [internal diameter (ID) ≤ 20 mm] compared with those with large-failed bioprostheses (ID > 20 mm) (33.2% vs. 40.5%, P = 0.01). Independent correlates for mortality included smaller-failed bioprosthetic valves [hazard ratio (HR) 1.07 (95% confidence interval (CI) 1.02-1.13)], age [HR 1.21 (95% CI 1.01-1.45)], and non-transfemoral access [HR 1.43 (95% CI 1.11-1.84)]. There were 40 reinterventions after ViV. Independent correlates for all-cause reintervention included pre-existing severe prosthesis-patient mismatch [subhazard ratio (SHR) 4.34 (95% CI 1.31-14.39)], device malposition [SHR 3.75 (95% CI 1.36-10.35)], EBEV [SHR 3.34 (95% CI 1.26-8.85)], and age [SHR 0.59 (95% CI 0.44-0.78)]. CONCLUSIONS: The size of the original failed valve may influence long-term mortality, and the type of the transcatheter valve may influence the need for reintervention after aortic ViV.

Five-Year Clinical and Echocardiographic Outcomes From the NOTION Randomized Clinical Trial in Patients at Lower Surgical Risk.

BACKGROUND: The NOTION trial (Nordic Aortic Valve Intervention) was designed to compare transcatheter aortic valve replacement (TAVR) with surgical aortic valve replacement (SAVR) in patients ≥70 years old with isolated severe aortic valve stenosis. Clinical and echocardiographic outcomes are presented after 5 years. METHODS: Patients were enrolled at 3 Nordic centers and randomized 1:1 to TAVR using the self-expanding CoreValve prosthesis (n=145) or SAVR using any stented bioprostheses (n=135). The primary composite outcome was the rate of all-cause mortality, stroke, or myocardial infarction at 1 year defined according to Valve Academic Research Consortium-2 criteria. RESULTS: Baseline characteristics were similar. The mean age was 79.1±4.8 years and mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 3.0%±1.7%. After 5 years, there were no differences between TAVR and SAVR in the composite outcome (Kaplan-Meier estimates 38.0% versus 36.3%, log-rank test P=0.86) or any of its components. TAVR patients had larger prosthetic valve area (1.7 cm2 versus 1.2 cm2, P<0.001) with a lower mean transprosthetic gradient (8.2 mm Hg versus 13.7 mm Hg, P<0.001), both unchanged over time. More TAVR patients had moderate/severe total aortic regurgitation (8.2% versus 0.0%, P<0.001) and a new pacemaker (43.7% versus 8.7%, P<0.001). Four patients had prosthetic reintervention and no difference was found for functional outcomes. CONCLUSIONS: These are currently the longest follow-up data comparing TAVR and SAVR in lower risk patients, demonstrating no statistical difference for major clinical outcomes 5 years after TAVR with a self-expanding prosthesis compared to SAVR. Higher rates of prosthetic regurgitation and pacemaker implantation were seen after TAVR. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT01057173.

Elastography and diffusion-weighted MRI in patients with testicular microlithiasis, normal testicular tissue, and testicular cancer: an observational study.

BACKGROUND: Ultrasound elastography is increasingly available in clinical practice. Recent studies showed higher velocity stiffness in testicular tumors compared to normal testicles. PURPOSE: To evaluate ultrasound elastography in combination with the apparent diffusion coefficient measurements in diffusion weighted (DW) magnetic resonance imaging (MRI) in testicles. DW can be a useful tool in evaluating testicular malignancies. However, the relationship between velocity stiffness and MRI diffusion is not well established. MATERIAL AND METHODS: We prospectively included 132 patients with testicular microlithiasis (n = 53), or normal testicular tissue (n = 53), or suspected for testicular cancer (n = 26). All 132 patients underwent ultrasonography including shear wave elastography and MRI diffusion coefficient examination of the scrotum. RESULTS: No clinically relevant difference in velocity stiffness was found between normal and testicles with microlithiasis. There was a significant difference in stiffness between patients with testicular microlithiasis (0.78 m/s), normal testicular tissue (0.77 m/s), and patients with testicular cancer (1.95 m/s) ( P ≤ 0.001). Similarly, there was a statistically significant difference in MRI diffusion values between patients with testicular microlithiasis (0.978 × 10-3 mm2 s-1), normal testicular tissue (0.929 × 10-3 mm2 s-1), and testicular cancers (0.743 × 10-3 mm2 s-1) ( P < 0.01). CONCLUSION: Patients with testicular microlithiasis had no malignant characteristics measured with shear wave elastography or MRI diffusion. MRI diffusion and elastography may be useful to preoperatively differentiate benign from malignant testicular lesions.

Mortality prediction after transcatheter treatment of failed bioprosthetic aortic valves utilizing various international scoring systems: Insights from the Valve-in-Valve International Data (VIVID).

BACKGROUND: Transcatheter Aortic Valve Implantation (TAVI) is commonly used to deploy new bioprosthetic valves inside degenerated surgically implanted aortic valves in high risk patients. The three scoring systems used to assess risk of postprocedural mortality are: Logistic EuroSCORE (LES), EuroSCORE II (ES II), and Society of Thoracic Surgeons (STS). OBJECTIVE: The purpose of this study is to analyze the accuracy of LES, ES II, and STS in estimating all-cause mortality after transcatheter aortic valve-in-valve (ViV) implantations, which was not assessed before. METHODS: Using the Valve-in-Valve International Data (VIVID) registry, a total of 1,550 patients from 110 centers were included. The study compared the observed 30-day overall mortality vs. the respective predicted mortalities calculated by risk scores. The accuracy of prediction models was assessed based on calibration and discrimination. RESULTS: Observed mortality at 30 days was 5.3%, while average expected mortalities by LES, ES II and STS were 29.49 (± 17.2), 14.59 (± 8.6), and 9.61 (± 8.51), respectively. All three risk scores overestimated 30-day mortality with ratios of 0.176 (95% CI 0.138-0.214), 0.342 (95% CI 0.264-0.419), and 0.536 (95% CI 0.421-0.651), respectively. 30-day mortality ROC curves demonstrated that ES II had the largest AUC at 0.722, followed by STS at 0.704, and LES at 0.698. CONCLUSIONS: All three scores overestimated mortality at 30 days with ES II showing the highest predictability compared to LES and STS; and therefore, should be recommended for ViV procedures. There is a need for a dedicated scoring system for patients undergoing ViV interventions.

The potential benefits from respiratory gating for breast cancer patients regarding target coverage and dose to organs at risk when applying strict dose limits to the heart: results from the DBCG HYPO trial.

PURPOSE: The potential benefits from respiratory gating (RG) compared to free-breathing (FB) regarding target coverage and dose to organs at risk for breast cancer patients receiving post-operative radiotherapy (RT) in the DBCG HYPO multicentre trial are reported. MATERIAL AND METHODS: Patients included in the DBCG HYPO trial were randomized between 50 Gy in 25 fractions (normofractionated) versus 40 Gy in 15 fractions (hypofractionated). A tangential forward field-in-field dose planning technique was used to cover the clinical target volume (CTV) with the intent to limit dose to the left anterior descending coronary artery (LADCA) to 20 Gy and 17 Gy in the normo- and hypofractionated arms, respectively. Treatment plan data for 1327 patients from four Danish centres was retrospectively analyzed. FB right-sided patients served as control group for the left-sided patients regarding CTV V95% (relative volume receiving at least 95% of the prescribed dose), mean heart dose (MHD) and mean lung dose (MLD). RESULTS: Median CTV V95% was for FB right-sided, FB left-sided and RG left-sided patients 94.6, 92.6 and 94.7% for normofractionated therapy, respectively, and 94.6, 91.8 and 94.4% for hypofractionated therapy and did not differ significantly for RG left-sided plans compared to FB right-sided in either study arm. CTV V95% was significantly lower for FB versus RG for left-sided plans in both arms. Median MHD was 0.7, 1.8 and 1.5 Gy (normofractionated therapy) versus 0.6, 1.5 and 1.2 Gy (hypofractionated therapy), respectively. The corresponding median MLD was 9.0, 8.3 and 7.3 Gy versus 7.3, 6.4 and 5.8 Gy, respectively. CONCLUSIONS: RG for left-sided breast cancer patients ensured similar CTV V95% as for FB right-sided patients. MLD was lower for RG due to the increased lung volume. MHD was generally low due to strict protocol-defined maximum dose to LADCA, but for left-sided patients RG led to significantly lower MHD.

Effect of permanent pacemaker on mortality after transcatheter aortic valve replacement.

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) is an established treatment for high-grade aortic valve stenosis in patients found unfit for open heart surgery. The method may cause cardiac conduction disorders requiring permanent pacemaker (PPM) implantation, and the long-term effect of PPM implantation remains ambiguous. Design One hundred sixty-eight patients who underwent TAVI from 2008 to 2012 were included. Patient characteristics, ECGs and PPM data were collected through medical records. Kaplan-Meier plots and Cox regression analysis were performed. RESULTS: Forty subjects were excluded, leaving 128 patients for final inclusion. 41 (32%) received a PPM (mean age 82 vs. 80 in patients without PPM, p = .06) within 30 days of the TAVI procedure. Median follow-up was ∼4 years and 37 (29%) died. One-year mortality was 14% for non-PPM patients vs. 2% in PPM patients, and mortality at 5yrs 70% vs. 54%, respectively. Kaplan-Meier survival analysis showed higher mortality in patients without PPM (p = .008). In multivariate survival analysis significant variables were: No PPM (HR 2.6; CI 1.1-6.2; p = .03), chronic obstructive pulmonary disease (HR 2.4; CI 1.2-5.0; p = .02) and either pre- or post-procedural chronic or paroxystic atrial fibrillation (HR 2.3; CI 1.2-4.7; p= .02). CONCLUSION: TAVI-patients with a PPM had better survival than patients in whom a PPM was not implanted.

Impact of chronic obstructive pulmonary disease on survival and symptoms of severe aortic valve stenosis.

BACKGROUND: As patients with severe aortic valve stenosis (AS) develop symptoms their survival decreases rapidly, if treated conservatively. Transcatheter aortic valve implantation (TAVI) has been introduced as a less invasive treatment alternative, especially in inoperable patients, who often have severe comorbidities, including chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Since the beginning of our TAVI program in March 2008, data on all 131 TAVI patients were prospectively and consecutively collected in this registry with complete follow-up. COPD was present in 37 patients. By January 2012 survival data were collected from the Danish Civil Registration System. Median follow-up duration was 559 days. RESULTS: Overall survival and survival from cardiac death was equivalent in both patients with and without COPD (p = 0.98 and p = 0.26) in the follow-up period. Further, patients with COPD had higher New York Heart Association (NYHA) class prior to intervention compared with those without (3.1 ± 0.5 vs. 2.9 ± 0.5, p = 0.02). In multivariate regression analysis COPD was associated with 30-day postoperative NYHA class (0.43; 95% confidence interval (CI): 0.10-0.75; p = 0.01), but not to NYHA class improvement from pre- to postintervention (0.25; 95% CI: - 0.12 to -0.63; p = 0.18). CONCLUSIONS: In patients with symptomatic severe AS treated with TAVI, the presence of COPD neither affects overall survival nor survival from cardiac death. Patients with COPD had, however, both higher pre- and postoperative NYHA class compared with patients without COPD, but NYHA class improvement from pre- to postintervention was equivalent in both groups.

Cancer risk among patients with congenital heart defects: a nationwide follow-up study.

OBJECTIVE: We aimed to assess cancer risk in congenital heart defect patients, with and without Down's syndrome, compared with the general population. METHODS: We identified all patients born and diagnosed with congenital heart defects from 1977 to 2008 using the Danish National Registry of Patients, covering all Danish hospitals. We compared cancer incidence in the congenital heart defect cohort with that expected in the general population (∼5.5 million) using the Danish Cancer Registry, and computed age- and gender-standardised incidence ratios. RESULTS: We identified 15,905 congenital heart defect patients, contributing a total of 151,172 person-years at risk; the maximum length of follow-up was 31 years (median 8 years). In all, 53 patients were diagnosed with cancer, including 30 female and 23 male patients (standardised incidence ratio = 1.63; 95% confidence interval: 1.22-2.13). Risks were increased for leukaemia, brain tumours, and basal cell carcinoma. After excluding 801 patients with Down's syndrome, the standardised incidence ratio was 1.19 (95% confidence interval: 0.84-1.64). In the subgroup of 5660 non-Down's syndrome patients undergoing cardiac surgery or catheter-based interventions, the standardised incidence ratio was 1.45 (95% confidence interval: 0.86-2.29). CONCLUSION: The overall risk of cancer among congenital heart defect patients without Down's syndrome was not statistically significantly elevated. Cancer risk in the congenital heart defect cohort as a whole, including patients with Down's syndrome, was increased compared with the general population, although the absolute risk was low. Studies with longer follow-up and more information on radiation doses are needed to further examine a potential cancer risk associated with diagnostic radiation exposure.

Transcatheter aortic valve implantation in failed bioprosthetic surgical valves.

IMPORTANCE: Owing to a considerable shift toward bioprosthesis implantation rather than mechanical valves, it is expected that patients will increasingly present with degenerated bioprostheses in the next few years. Transcatheter aortic valve-in-valve implantation is a less invasive approach for patients with structural valve deterioration; however, a comprehensive evaluation of survival after the procedure has not yet been performed. OBJECTIVE: To determine the survival of patients after transcatheter valve-in-valve implantation inside failed surgical bioprosthetic valves. DESIGN, SETTING, AND PARTICIPANTS: Correlates for survival were evaluated using a multinational valve-in-valve registry that included 459 patients with degenerated bioprosthetic valves undergoing valve-in-valve implantation between 2007 and May 2013 in 55 centers (mean age, 77.6 [SD, 9.8] years; 56% men; median Society of Thoracic Surgeons mortality prediction score, 9.8% [interquartile range, 7.7%-16%]). Surgical valves were classified as small (≤21 mm; 29.7%), intermediate (>21 and <25 mm; 39.3%), and large (≥25 mm; 31%). Implanted devices included both balloon- and self-expandable valves. MAIN OUTCOMES AND MEASURES: Survival, stroke, and New York Heart Association functional class. RESULTS: Modes of bioprosthesis failure were stenosis (n = 181 [39.4%]), regurgitation (n = 139 [30.3%]), and combined (n = 139 [30.3%]). The stenosis group had a higher percentage of small valves (37% vs 20.9% and 26.6% in the regurgitation and combined groups, respectively; P = .005). Within 1 month following valve-in-valve implantation, 35 (7.6%) patients died, 8 (1.7%) had major stroke, and 313 (92.6%) of surviving patients had good functional status (New York Heart Association class I/II). The overall 1-year Kaplan-Meier survival rate was 83.2% (95% CI, 80.8%-84.7%; 62 death events; 228 survivors). Patients in the stenosis group had worse 1-year survival (76.6%; 95% CI, 68.9%-83.1%; 34 deaths; 86 survivors) in comparison with the regurgitation group (91.2%; 95% CI, 85.7%-96.7%; 10 deaths; 76 survivors) and the combined group (83.9%; 95% CI, 76.8%-91%; 18 deaths; 66 survivors) (P = .01). Similarly, patients with small valves had worse 1-year survival (74.8% [95% CI, 66.2%-83.4%]; 27 deaths; 57 survivors) vs with intermediate-sized valves (81.8%; 95% CI, 75.3%-88.3%; 26 deaths; 92 survivors) and with large valves (93.3%; 95% CI, 85.7%-96.7%; 7 deaths; 73 survivors) (P = .001). Factors associated with mortality within 1 year included having small surgical bioprosthesis (≤21 mm; hazard ratio, 2.04; 95% CI, 1.14-3.67; P = .02) and baseline stenosis (vs regurgitation; hazard ratio, 3.07; 95% CI, 1.33-7.08; P = .008). CONCLUSIONS AND RELEVANCE: In this registry of patients who underwent transcatheter valve-in-valve implantation for degenerated bioprosthetic aortic valves, overall 1-year survival was 83.2%. Survival was lower among patients with small bioprostheses and those with predominant surgical valve stenosis.

Temporal Trends in Patient Characteristics and Outcomes of Transcatheter Aortic Valve Implantation and Surgical Aortic Valve Replacement: A Nationwide Study.

With increased use of transcatheter aortic valve implantation (TAVI) in treatment of aortic stenosis, it is important to evaluate real life data trends in outcomes. This nationwide register-based study aimed to present an outlook on temporal trends in characteristics and outcomes, including mortality. First-time consecutive Danish patients who underwent TAVI from 2010 to 2019 were included in this study. The chi-square and Kruskal-Wallis tests were performed to assess the differences in the characteristics over time and Cochrane-Armitage trend tests were used to examine changes in complications and mortality. Between 2010 and 2019, 4,847 patients (54.6% men, median age 82 [quartile 1 to quartile 3: 77 to 85] years) underwent first-time TAVI. A statistically significant decrease over time was observed for preprocedural hypertension, ischemic heart disease, and heart failure, whereas preexisting chronic obstructive lung disease and preprocedural pacemaker remained stable. We observed a significant decrease in 30- and 90-day postoperative preprocedural pacemaker implantation from 2011 to 2017, with 15.1% and 15.9% in 2011 and 8.6% and 8.9% in 2017, respectively. The incidence of for 30- and 90-day heart failure significantly decreased from 19.3% and 20.3% to 8.5% and 9.1%, respectively. We observed significant changes for 30-day atrial fibrillation, whereas the changes over time for 90-day atrial fibrillation and 30- and 90-day stroke/transient ischemic attack remained insignificant. The all-cause mortality within 30- and 90 days significantly decreased over time from 6.7% and 9.2% in 2011 to 1.5% and 2.7% in 2019 and 2016, respectively. In conclusion, this national study provides general insight on the trends of complications and mortality of TAVI, demonstrating significant reductions over time.

Impact of mandatory preoperative dental screening on post-procedural risk of infective endocarditis in patients undergoing transcatheter aortic valve implantation: a nationwide retrospective observational study.

Background: Guidelines recommend preoperative dental screening (PDS) prior to cardiac valve surgery, to reduce the incidence of prosthetic valve infective endocarditis (IE). However, limited data support these recommendations, particular in patients undergoing transcatheter aortic valve implantation (TAVI). We aimed to investigate the effect of mandatory PDS on risk of IE in patients undergoing TAVI. Methods: In this observational study, a total of 1133 patients undergoing TAVI in Western-Denmark from 2020 to 2022 were included. Patients were categorized based on two implemented PDS practices: mandatory PDS (MPDS group), and no referral for PDS (NPDS group). Outcome data were retrieved from Danish registries and confirmed using medical records. The primary outcome was incidence of IE. Secondary outcomes were all-cause mortality and composite outcome of all-cause mortality and IE. Findings: Of 568 patients in the MPDS group 126 (22.2%) underwent subsequent oral dental surgery, compared to 8 (1.4%) among 565 patients in the NPDS group. During a median follow-up of 1.9 years (interquartile range 1.4-2.5 years), 31 (2.7%) developed IE. The yearly incidence IE rate was 1.4% (0.8-2.3) and 1.5% (0.8-2.4) in MPDS and NPDS, respectively, p = 0.86. All-cause mortality rates were similar between groups (estimated 2-year overall mortality of 6.7% (4.8-9.2) vs. 4.7% (3.2-6.9), MPDS and NPDS, respectively, p = 0.15). Consistent findings were found in 712 propensity score-matched patients. Interpretation: Mandatory PDS did not demonstrate reduced risk of IE or all-cause mortality compared to targeted PDS in patients undergoing TAVI. Funding: The funder had no role in the study design, data management, or writing.

Treatment planning for patients with low rectal cancer in a multicenter prospective organ preservation study.

BACKGROUND: Non-surgical management of rectal cancer relies on (chemo)radiotherapy as the definitive treatment modality. This study reports and evaluates the clinical high dose radiotherapy treatment plans delivered to patients with low resectable rectal cancer in a Danish multicenter trial. METHODS: The Danish prospective multicenter phase II Watchful Waiting 2 trial (NCT02438839) investigated definitive chemoradiation for non-surgical management of low rectal cancer. Three Danish centers participated in the trial and committed to protocol-specified treatment planning and delivery requirements. The protocol specified a dose of 50.4 Gy in 28 fractions to the elective volume (CTV-/PTV-E) and a concomitant boost of 62 Gy in 28 fractions to the primary target volume (CTV-/PTV-T). RESULTS: The trial included 108 patients, of which 106 treatment plans were available for retrospective analysis. Dose coverage planning goals for the main target structures were fulfilled for 94% of the treatment plans. However, large intercenter differences in doses to organs-at-risk (OARs) were seen, especially for the intestines. Five patients had a V60Gy>10 cm3 for the intestines and two patients for the bladder. CONCLUSION: Prescribed planning goals for target coverage were fulfilled for 94% of the treatment plans, however analysis of OAR doses and volumes indicated intercenter variations. Dose escalation to 62 Gy (as a concomitant boost to the primary tumor) introduced no substantial high dose volumes (>60 Gy) to the bladder and intestines. The treatment planning goals may be used for future prospective evaluation of highdose radiotherapy for organ preservation for low rectal cancer.

Quality assessment of radiotherapy in the prospective randomized SENOMAC trial.

BACKGROUND AND PURPOSE: Recommendations for regional radiotherapy (RT) of sentinel lymph node (SLN)-positive breast cancer are debated. We here report a RT quality assessment of the SENOMAC trial. MATERIALS AND METHODS: The SENOMAC trial randomized clinically node-negative breast cancer patients with 1-2 SLN macrometastases to completion axillary lymph node dissection (cALND) or SLN biopsy only between 2015-2021. Adjuvant RT followed national guidelines. RT plans for patients included in Sweden and Denmark until June 2019 were collected (N = 1176) and compared to case report forms (CRF). Dose to level I (N = 270) and the humeral head (N = 321) was analyzed in detail. RESULTS: CRF-data and RT plans agreed in 99.3 % (breast/chest wall) and in 96.6 % of patients (regional RT). Congruence for whether level I was an intended RT target was lower (78 %). In accordance with Danish national guidelines, level I was more often an intended target in the SLN biopsy only arm (N = 334/611, 55 %,) than in the cALND arm (N = 174/565, 31 %,). When an intended target, level I received prescribed dose to 100 % (IQR 98-100 %) of the volume. However, even when not an intended target, full dose was delivered to > 80 % of level I (IQR 75-90 %). The intentional inclusion of level I in the target volume more than doubled the dose received by ≥ 50 % of the humeral head. CONCLUSION: Congruence between CRF data and RT plans was excellent. Level I received a high dose coverage even when not intentionally included in the target. Including level I in target significantly increased dose to the humeral head.