Citations

PURPOSE The COVID-19 pandemic has profoundly affected cancer care worldwide, including radiation therapy (RT) for breast cancer (BC), because of risk-based resource allocation. We report the evolution of international breast RT practices during the beginning of the pandemic, focusing on differences in treatment recommendations between countries. MATERIALS AND METHODS Between July and November 2020, a 58-question survey was distributed to radiation oncologists (ROs) through international professional societies. Changes in RT decision making during the first surge of the pandemic were evaluated across six hypothetical scenarios, including the management of ductal carcinoma in situ (DCIS), early-stage, locally advanced, and metastatic BC. The significance of changes in responses before and during the pandemic was examined using chi-square and McNemar-Bowker tests. RESULTS One thousand one hundred three ROs from 54 countries completed the survey. Incomplete responses (254) were excluded from the analysis. Most respondents were from the United States (285), Japan (117), Italy (63), Canada (58), and Brazil (56). Twenty-one percent (230) of respondents reported treating at least one patient with BC who was COVID-19–positive. Approximately 60% of respondents reported no change in treatment recommendation during the pandemic, except for patients with metastatic disease, for which 57.7% (636/1,103; P < .0005) changed their palliative practice. Among respondents who noted a change in their recommendation during the first surge of the pandemic, omitting, delaying, and adopting short-course RT were the most frequent changes, with most transitioning to moderate hypofractionation for DCIS and early-stage BC. CONCLUSION Early in the COVID-19 pandemic, significant changes in global RT practice patterns for BC were introduced. The impact of published results from the FAST FORWARD trial supporting ultrahypofractionation likely confounded the interpretation of the pandemic's independent influence on RT delivery.

Abstract Background Hearing loss is a risk factor for dementia; whether the association is causal or due to a shared pathology is unknown. We estimated the association of brain β-amyloid with hearing, hypothesizing no association. As a positive control, we quantified the association of hearing loss with neurocognitive test performance. Methods Cross-sectional analysis of Atherosclerosis Risk in Communities-Positron Emission Tomography study data. Amyloid was measured using global cortical and temporal lobe standardized uptake value ratios (SUVRs) calculated from florbetapir-positron emission tomography scans. Composite global and domain-specific cognitive scores were created from 10 neurocognitive tests. Hearing was measured using an average of better-ear air conduction thresholds (0.5–4 kHz). Multivariable-adjusted linear regression estimated mean differences in hearing by amyloid and mean differences in cognitive scores by hearing, stratified by race. Results In 252 dementia-free adults (72–92 years, 37% Black race, and 61% female participants), cortical or temporal lobe SUVR was not associated with hearing (models adjusted for age, sex, education, and APOE ε4). Each 10 dB HL increase in hearing loss was associated with a 0.134 standard deviation lower mean global cognitive factor score (95% CI: −0.248, −0.019), after adjustment for demographic and cardiovascular factors. Observed hearing-cognition associations were stronger in Black versus White participants. Conclusions Amyloid is not associated with hearing, suggesting that pathways linking hearing and cognition are independent of this pathognomonic Alzheimer’s-related brain change. This is the first study to show that the impact of hearing loss on cognition may be stronger in Black versus White adults.

Abstract Background: DEPendency of association on the number of Top Hits (DEPTH) is an approach to identify candidate susceptibility regions by considering the risk signals from overlapping groups of sequential variants across the genome. Methods: We applied a DEPTH analysis using a sliding window of 200 SNPs to colorectal cancer data from the Colon Cancer Family Registry (CCFR; 5,735 cases and 3,688 controls), and Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO; 8,865 cases and 10,285 controls) studies. A DEPTH score &gt; 1 was used to identify candidate susceptibility regions common to both analyses. We compared DEPTH results against those from conventional genome-wide association study (GWAS) analyses of these two studies as well as against 132 published susceptibility regions. Results: Initial DEPTH analysis revealed 2,622 (CCFR) and 3,686 (GECCO) candidate susceptibility regions, of which 569 were common to both studies. Bootstrapping revealed 40 and 49 candidate susceptibility regions in the CCFR and GECCO data sets, respectively. Notably, DEPTH identified at least 82 regions that would not be detected using conventional GWAS methods, nor had they been identified by previous colorectal cancer GWASs. We found four reproducible candidate susceptibility regions (2q22.2, 2q33.1, 6p21.32, 13q14.3). The highest DEPTH scores were in the human leukocyte antigen locus at 6p21 where the strongest associated SNPs were rs762216297, rs149490268, rs114741460, and rs199707618 for the CCFR data, and rs9270761 for the GECCO data. Conclusions: DEPTH can identify candidate susceptibility regions for colorectal cancer not identified using conventional analyses of larger datasets. Impact: DEPTH has potential as a powerful complementary tool to conventional GWAS analyses for discovering susceptibility regions within the genome.

AbstractObjectivesAlthough hemispheric surgeries are among the most effective procedures for drug‐resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1‐, 2‐, and 5‐years post‐hemispherectomy.MethodsRetrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time‐to‐seizure recurrence. A multivariate Cox proportional‐hazards regression model was developed to predict the likelihood of post‐hemispheric surgery seizure freedom at three time points (1‐, 2‐ and 5‐ years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops‐calculator.com/).ResultsThe selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non‐hemispheric resective surgery, and contralateral fluorodeoxyglucose–positron emission tomography [FDG‐PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time‐to‐seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG‐PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non‐lesional MRI, non‐stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%.SignificanceOnline calculators are useful, cost‐free tools that can assist physicians in risk estimation and inform joint decision‐making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms “nonalcoholic” and “fatty” were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction–associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction–associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction–associated steatotic liver disease, who consume greater amounts of alcohol per week (140–350 g/wk and 210–420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.

Background: Mortality remains high in patients with ST-segment–elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS), and early reperfusion has been shown to improve outcomes. We analyzed the association between first medical contact (FMC)-to-percutaneous coronary angiography time with mortality and major adverse cardiovascular events among patients with STEMI with and without CS. Methods: We performed a retrospective analysis of the Vancouver Coastal Health Authority STEMI registry, including all patients with STEMI who received primary percutaneous coronary angiography between January 1, 2010, and December 31, 2020, and stratified them by presence or absence of CS at hospital arrival. The primary outcome was in-hospital mortality, the secondary outcome was in-hospital major adverse cardiovascular events, defined as a composite of the first occurrence of mortality, cardiac arrest, heart failure, intracerebral hemorrhage, cerebrovascular accident, or reinfarction. Mixed effects logistic regression with restricted cubic splines was used to estimate the relationships between FMC-to-device time and the outcomes in the CS and non-CS groups. Results: 2929 patients were included, 9.4% (n=275) had CS. Median FMC-to-device time was 113.5 (interquartile range, 93.0–145.0) and 103.0 (interquartile range, 85.0–130.0) minutes for patients with CS and without CS, respectively. More patients with CS had FMC-to-device times above guideline recommendations (76.6% versus 54.1%, P <0.001). Between 60 and 90 minutes, for each 10-minute increase in FMC-to-device time, absolute mortality for patients with CS increased by 4% to 7%, whereas for patients without CS, it increased by <0.5%. Conclusions: Among patients with STEMI undergoing primary percutaneous coronary angiography, reperfusion delays among patients with CS are associated with significantly worse outcomes. Strategies to reduce FMC-to-device times for patients with STEMI presenting with CS are required.

Abstract Funding Acknowledgements Type of funding sources: None. Background Severe aortic-stenosis (AS) is the guideline-based indication for aortic-valve-replacement (AVR) performance, which has markedly increased with transcatheter approaches, suggesting possible increasing AS incidence. However, reported secular trends of AS incidence remain contradictory, uncertain and lacking quantitative Doppler-Echocardiographic ascertainment. Thus, population-based trends in presentation, treatment and outcome are unknown. Methods All adults residents our County (MN,USA) diagnosed with incident (first-diagnosis) severe AS based on quantitative Doppler-Echocardiography (aortic-valve-area≤1cm2, aortic-valve-area-index≤0.6cm2/m2, mean-gradient≥40mmHg, peak-velocity≥4m/s, Doppler-velocity-index≤0.25) between 1997–2016, were accounted for and trends for incidence, presentation, treatment and outcome analysed. Results Incident severe-AS was diagnosed in 1069 community-residents over 20-years. Incidence-rate was 52.5[49.4–55.8] per 100.000 patient/year, slightly higher in male vs. female and was almost unchanged after age and sex adjustment for the US population 53.8[50.6–57.0] per-100000 residents/year. Over 20-years severe AS-incidence remained stable (p = 0.20) but absolute-burden of incident-cases markedly increased (p = 0.0004) due to population growth. Incidence-trend differed by sex, stable in men (incidence-rate-ratio 0.99, p = 0.72) but declining in women: (incidence-rate-ratio 0.93, p = 0.024). AS clinical-presentation, age, symptoms, comorbidity, ventricular size/function, valve-area-index, low-flow or low-ejection-fraction AS, remained stable. Over the study 20 years, AVR performance grew (1997–2001 to 2012–2016, at 3-month:14% to 21%, p = 0.02; at 1-year 19% to 33%,p&lt;0.0001), and was more prompt (from 1.3[0.11–3.3]years in 1997–2001 to 0.48[0.15–2.11]years in 2013–2016, p = 0.001) but severe AS undertreatment remained prominent (&gt;40%). Early-AVR (within 3-months) was associated with survival benefit (adjusted-hazard-ratio 0.55[0.42–0.71], p&lt;0.0001) stable throughout the 20-years. Despite these improvements, overall mortality, 8.3% within 3-months, 17.8% within 1-year, 36% within 3-years, was swift, considerable and unabated (all p≥0.44) throughout the 20-year study. Conclusion Over 20 years, the population incidence of severe-AS remained stable with increased absolute case-burden purely related to population growth. Despite stable severe-AS presentation, AVR performance grew notably, but while declining, undertreatment remained substantial and disease-lethality did not decline. These findings have important population-health management implications.

Neoadjuvant chemotherapy (NAC) increases rates of successful breast-conserving surgery (BCS) in patients with breast cancer. However, some studies suggest that BCS after NAC may confer an increased risk of locoregional recurrence (LRR). We assessed LRR rates and locoregional recurrence-free survival (LRFS) in patients enrolled on I-SPY2 (NCT01042379), a prospective NAC trial for patients with clinical stage II to III, molecularly high-risk breast cancer. Cox proportional hazards models were used to evaluate associations between surgical procedure (BCS vs mastectomy) and LRFS adjusted for age, tumor receptor subtype, clinical T category, clinical nodal status, and residual cancer burden (RCB). In 1462 patients, surgical procedure was not associated with LRR or LRFS on either univariate or multivariate analysis. The unadjusted incidence of LRR was 5.4% after BCS and 7.0% after mastectomy, at a median follow-up time of 3.5 years. The strongest predictor of LRR was RCB class, with each increasing RCB class having a significantly higher hazard ratio for LRR compared with RCB 0 on multivariate analysis. Triple-negative receptor subtype was also associated with an increased risk of LRR (hazard ratio: 2.91, 95% CI: 1.8–4.6, P < 0.0001), regardless of the type of operation. In this large multi-institutional prospective trial of patients completing NAC, we found no increased risk of LRR or differences in LRFS after BCS compared with mastectomy. Tumor receptor subtype and extent of residual disease after NAC were significantly associated with recurrence. These data demonstrate that BCS can be an excellent surgical option after NAC for appropriately selected patients.

Introduction: Repeated 6MWT in clinic are inconvenient for patients and disruptive to usual clinic throughput. Digital measures may be a means to overcome these challenges and reliably measure functional capacity. Methods: As part of an observational clinical trial (NCT04191356), during an 8-week observation period, patients with heart failure (HF) utilize arm-band biosensors (Biofourmis Everion®) for at least 15 hours daily while carrying out daily activities and complete an in-clinic investigator-guided 6MWT on the first and last days of participation. Interim data (N=30, age 56.17 ± 11.26; 24 males; 3 NYHA I, 25 NYHA II, 2 NYHA III) are used for validation, where the distance of baseline 6MWT is used as reference standard. Results: Passive 6MWT, which is the maximum 6-minute step count derived from daily accelerometer data (Fig 1), is strongly correlated with the reference standard (R=0.7501, P<0.0001, N=30) (Fig 2). Further analysis (Fig 2) reveals that regardless of the duration of the step count, the digital measures consistently have strong correlations with the reference standard, with the highest correlation obtained by Passive 10MWT (R=0.7746, P<0.0001, N=30). Conclusions: Early data highlights that accelerometer data collected during daily activities appears to indicate functional capacity of HF patients. Continued data will validate digital measures against various patient outcomes. Fig 1 Aggregation of Passive 6MWT from step count recorded during daily activities Fig 2 Correlation between accelerometer-derived passive step count digital measures and distance manually measured during baseline investigator-guided 6MWT as reference standard (N=30)