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The NCCN Guidelines for Breast Cancer include up-to-date guidelines for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, male breast cancer, and breast cancer during pregnancy. These guidelines are developed by a multidisciplinary panel of representatives from NCCN Member Institutions with breast cancer-focused expertise in the fields of medical oncology, surgical oncology, radiation oncology, pathology, reconstructive surgery, and patient advocacy. These NCCN Guidelines Insights focus on the most recent updates to recommendations for adjuvant systemic therapy in patients with nonmetastatic, early-stage, hormone receptor-positive, HER2-negative breast cancer.

Recently, children with temporal lobe epilepsy (TLE) were found to be at risk of accelerated long-term forgetting (ALF). In this study, we examined the temporal trajectory of ALF, while exploring the relationship between ALF, executive skills, and epilepsy variables. Fifty-one children, (23 with TLE and 28 typically developing) completed a battery of neuropsychological tests of verbal and visual memory, executive skills, and two experimental memory tasks (verbal and visual) involving recall after short (30-min) and extended (1-day and 2-week) delays. Side of seizure focus and hippocampal integrity were considered. On the visual task (Scene Memory), children with TLE performed comparably to typically developing children following a 30-min and 1-day delay, although worse than typically developing children at 2 weeks: ALF was observed in children with right TLE focus. The two groups did not differ on the experimental verbal memory task. Children with TLE also had worse performance than typically developing children on standardized verbal memory test and on tests of executive skills (i.e., verbal generativity, inhibition, working memory, complex attention). Only complex attention was associated with visual ALF. ALF was present for visuo-spatial materials in children with TLE at two weeks, and children with right TLE were most susceptible. A relationship was identified between complex attention and long-term forgetting. The findings extend our understanding of difficulties in long-term memory formation experienced by children with TLE.

About one-third of people with epilepsy experience comorbid depression. The present study examined outcomes of a distance-delivery group intervention program designed to improve emotional well-being. Participants were 55 adults with epilepsy and self-reported depressive symptoms who were randomly assigned to take part in either a mindfulness-based cognitive behavioral therapy (CBT) program (UPLIFT, n = 20), an epilepsy information and self-management program (EpINFO, n = 24) that served as an active control group, or a wait-list control (WLC) group (n = 11). The Quick Inventory of Depressive Symptomatology (QIDS), Neurological Disorders Depression Inventory for Epilepsy (NDDIE), and the psychological health subscale of the World Health Organization Quality of Life (WHOQOL-BREF) scale were used to assess depression and psychological quality of life before and after treatment, and at short-term (six months) and long-term follow-up (one year) upon program completion. From pre- to posttreatment, a main effect of time was found, with participants in both the UPLIFT and EpINFO groups having reported to a similar degree a significant decrease in depressive symptoms and improved psychological health, improvements that were not seen in the WLC group. The time by group interaction effect was not significant. The effects seen at posttreatment in the UPLIFT and EpINFO groups remained at six months and one year after treatment. These data suggest that distance-delivery group intervention programs are effective at improving depression and psychological quality of life, with the EpINFO program offering benefits similar to the UPLIFT program.

Objective In adults with left-sided epilepsy, reorganized language may “crowd out” right-hemisphere visual–spatial skills, with relative sparing of language (i.e., the crowding hypothesis). However, this effect has not consistently been demonstrated in pediatric epilepsy studies. The objective of this study was to investigate the crowding hypothesis using a heterogeneous sample of children with intractable epilepsy and typical (left) language dominance or atypical (right or bilateral) language dominance. We examined the relative contributions of seizure onset (before or after age 5), handedness (right versus left), seizure localization (temporal versus extratemporal), as well as language dominance on verbal versus visual cognitive skills. Method We retrospectively analyzed neuropsychology assessment results from a sample of 91 children who completed presurgical evaluation at the Hospital for Sick Children in Toronto, Canada (34 with typical language, 57 with atypical language, mean age = 12 years). We considered a selection of verbal skills (naming, vocabulary knowledge, verbal abstract reasoning) and visual skills (visual–motor integration, block construction, visual abstract reasoning). Results Consistent with several previous adult studies supporting the crowding hypothesis, univariate analyses showed that the typical and atypical language groups were comparable on the measures of vocabulary knowledge and abstract verbal reasoning whereas the atypical language group produced lower scores across visual measures. Multivariate analyses (taking into account language dominance and associated factors) showed that language dominance was the strongest predictor of performance on two of three visual measures whereas language dominance was not a significant predictor of performance on most verbal measures. Unexpectedly, both sets of analyses indicated that the atypical language group had poorer naming abilities than the typical language group. Significance Our data provide some evidence of right-hemisphere functional crowding effects in a heterogeneous sample of children with intractable left-sided epilepsy. Specifically, those with atypical versus typical language dominance showed poorer visual–motor integration and visual–motor problem-solving skills, with comparable scores on certain verbal measures. It is critical that potential crowding effects be considered when interpreting the neuropsychological profiles of children being evaluated for epilepsy surgery.

254 Background: As the combination of systemic and targeted chemotherapies is associated with severe adverse side effects and long-term health complications, there is interest in reducing treatment intensity for patients with early-stage breast cancer (EBC). Currently, this approach is being described as “de-escalation,” though there is some concern that this language and framing are not well understood or preferred by patients. Methods: We collected qualitative interview data from twenty-four patients with Stage II-III breast cancer and sixteen patient advocates. Interviews explored interest in participation in clinical trials testing reduced amounts of chemotherapy, reactions to the word “de-escalation,” and preferred ways to describe this approach and its anticipated benefits. Interviews were audio-recorded and transcribed, and researchers used qualitative content analysis to code for dominant themes. Results: Twenty-three participants (57.5%) expressed interest in participating in a trial of reduced chemotherapy. However, 60% of participants had a negative response to the word “de-escalation,” including 78% of respondents that said they were interested in the concept. To describe this approach, respondents tend to prefer words like “personalization,” “optimization,” or “reduced chemotherapy.” Participants also expressed the importance of provider-patient communication, clear and simple language, sharing the decision-making process, and continued support throughout and after treatment in their consideration of trials testing lower amounts of chemotherapy. Conclusions: Among individuals with EBC, there is significant interest in alleviating treatment-related toxicity by reducing chemotherapeutic intensity. Patients are more apt to feel comfortable participating in trials testing this approach if they are framed in terms of customizing treatment to the individual patient and added benefit—reduced toxicities, higher quality of life during treatment and lower risk of long-term complications—rather than in terms of taking treatments away or doing less than the standard of care. “De-escalation” is not an ideal word to describe these trials as many associate this word with giving up in the war against cancer. Instead, participants prefer positive, patient-centered language. This information will be useful to providers in considering how best to describe de-escalation clinical trials to eligible patients in ways that avoid therapeutic misconception and facilitate the shared decision-making process regarding treatment.

Decelerated resting cortical oscillations, high-frequency activity, and enhanced cross-frequency interactions are features of focal epilepsy. The association between electrophysiological signal properties and neurocognitive function, particularly following resective surgery, is, however, unclear. In the current report, we studied intraoperative recordings from intracranial electrodes implanted in seven children with focal epilepsy and analyzed the spectral dynamics both before and after surgical resection of the hypothesized seizure focus. The associations between electrophysiological spectral signatures and each child's neurocognitive profiles were characterized using a partial least squares analysis. We find that extent of spectral alteration at the periphery of surgical resection, as indexed by slowed resting frequency and its acceleration following surgery, is associated with baseline cognitive deficits in children. The current report provides evidence supporting the relationship between altered spectral properties in focal epilepsy and neuropsychological deficits in children. In particular, these findings suggest a critical role of disrupted thalamocortical rhythms, which are believed to underlie the spectral alterations we describe, in both epileptogenicity and neurocognitive function.

Paediatric epilepsy surgery is an increasingly used evidence-based management option with low risks for complications. Developments in neuroimaging techniques and other advanced diagnostics have widened the spectrum of children who could benefit from the procedure, and surgery is now considered a standard management approach for epilepsy. Available data indicate that early surgery improves outcomes. Despite these considerable advances, epilepsy surgery in children is still underused. In this Review, we summarise the indications, patient selection, principles of presurgical investigations, optimal timing, and types of epilepsy surgery. We also examine comprehensive outcomes after surgery, including seizure outcomes, complications, cognition, neurodevelopment, vocational outcome, and health-related quality of life of children and their parents. Successful epilepsy surgery could lead to improvement in all these areas. Children should, therefore, be referred early for evaluation in an appropriately competent centre.

The neural mechanisms that underlie selective attention in children are poorly understood. By administering a set-shifting task to children with intracranial electrodes stereotactically implanted within anterior cingulate cortex (ACC) for epilepsy monitoring, we demonstrate that selective attention in a set-shifting task is dependent upon theta-band phase resetting immediately following stimulus onset and that the preferred theta phase angle is predictive of reaction time during attentional shift. We also observe selective enhancement of oscillatory coupling between the ACC and the dorsal attention network and decoupling with the default mode network during task performance. When transient focal epileptic activity occurs around the time of stimulus onset, phase resetting is impaired, connectivity changes with attentional and default mode networks are abolished, and reaction times are prolonged. The results of the present work highlight the fundamental mechanistic role of oscillatory phase in ACC in supporting attentional circuitry and present novel opportunities to remediate attention deficits in children with epilepsy.

Background Fear of recurrence (FoR) is a prevalent concern among breast cancer survivors (BCS), yet few accessible interventions exist. This study evaluated a targeted eHealth intervention, “FoRtitude,” to reduce FoR using cognitive behavioral skills training and telecoaching. Methods BCS (N = 196) were recruited from an academic medical center and 3 National Cancer Institute Community Oncology Research Program community sites, had stage 0-III breast cancer, were 1-10 years postprimary treatment, with moderate to high FoR and familiarity with the internet. Using the Multiphase Optimization Strategy, participants were independently randomly assigned to 3 cognitive behavioral skills (relaxation, cognitive restructuring, worry practice) vs an attention control condition (health management content [HMC]) and to telecoaching (motivational interviewing) vs no telecoaching. Website content was released across 4 weeks and included didactic lessons, interactive tools, and a text-messaging feature. BCS completed the Fear of Cancer Recurrence Inventory at baseline and at 4 and 8 weeks. Fear of Cancer Recurrence Inventory scores over time were compared using mixed-effects models. All statistical tests were 2-sided. Results FCRI scores [SD] decreased statistically significantly from baseline to postintervention (T0 = 53.1 [17.4], T2 = 41.9 [16.2], P Conclusions BCS experienced statistically significant reductions in FoR postintervention, but improvements were comparable between CBT and attention controls. Telecoaching improved adherence and retention. Future research is needed on optimal integration of CBT and HMC, dose, and features of eHealth delivery that contributed to reducing FoR. In the COVID-19 era, remote delivery has become even more essential for reaching survivors struggling with FoR.

Background As the combination of systemic and targeted chemotherapies is associated with severe adverse side effects and long-term health complications, there is interest in reducing treatment intensity for patients with early stage breast cancer (EBC). Clinical trials are needed to determine if it is feasible to reduce treatment intensity while maintaining 3-year recurrence-free survival of greater than 92%. In order to recruit patients for de-implementation trials, it is important to understand patient perspectives on barriers and facilitators to reducing treatment intensity. Methods We collected qualitative interview data from patients with Stage II-III breast cancer (N=24) and patient advocates (N=16). Interviews explored interest in de-implementation trial participation and identified potential barriers and facilitators to participation. 17 participants were asked about the potential impact of COVID-19 on de-implementation efforts. Interviews were audio-recorded and transcribed, and researchers used qualitative content analysis (NVIVO and Atlas.ti) to code for dominant themes. Results 17 participants (42.5%) expressed interest in participating in a trial of reduced chemotherapy. Barriers to reducing chemotherapy included (1) fear of recurrence and inefficacy, (2) preference for aggressive treatment, (3) disinterest in clinical trials, (4) lack of information about expected outcomes, (5) fear of regret, and (6) having young children. Facilitators included (1) avoiding physical toxicity, (2) understanding the scientific rationale of reducing chemotherapy, (3) confidence in providers, (4) consistent monitoring and the option to increase dosage, (5) fewer financial and logistical challenges, and (6) contributing to scientific knowledge. Of those asked, nearly all participants said they would be more motivated to reduce treatment intensity in the context of Covid-19, primarily in order to avoid exposure to the virus while receiving treatment. Conclusions We recommend framing de-implementation strategies and recruitment to trials in terms of customizing treatment to the individual patient and added benefit—reduced toxicities, higher quality of life during treatment and lower risk of long-term complications—rather than in terms of taking treatments away or doing less than the standard of care. Doctor-patient rapport and provider support will be crucial in this process.

Life is a journey of choices, known to the research community as risk/benefit analyses and to the lay community as choosing the best ways to live as successfully as possible with success being individually defined. For those of us with chemo-induced neuropathy, the neuropathy is a sequalae of one of those hard choices. A question we need to consider is if the choice was an informed one. Did we know both the negative and positive consequences of the choice to have chemotherapy and how do we live with the consequences of our choice? We dealt with the short-term negative effects such as profound nausea and hair loss. The question now becomes dealing with the long-term effects. Some of us were unaware that all side effects do not end when treatment ends.

Working memory (WM) deficits are pervasive co-morbidities of epilepsy. Although the pathophysiological mechanisms underpinning these impairments remain elusive, it is thought that WM depends on oscillatory interactions within and between nodes of large-scale functional networks. These include the hippocampus and default mode network as well as the prefrontal cortex and frontoparietal central executive network. Here, we review the functional roles of neural oscillations in subserving WM and the putative mechanisms by which epilepsy disrupts normative activity, leading to aberrant oscillatory signatures. We highlight the particular role of interictal epileptic activity, including interictal epileptiform discharges and high frequency oscillations (HFOs) in WM deficits. We also discuss the translational opportunities presented by greater understanding of the oscillatory basis of WM function and dysfunction in epilepsy, including potential targets for neuromodulation.

Aim To simultaneously evaluate long-term outcomes of children with drug-resistant epilepsy (DRE) across multiple cognitive domains and compare the characteristics of participants sharing a similar cognitive profile. Method Participants were adolescents and young adults (AYAs) diagnosed with DRE in childhood, who completed a comprehensive neuropsychological battery evaluating intelligence, memory, academic, and language skills at the time of surgical candidacy evaluation and at long-term follow-up (4-11y later). Hierarchical k-means clustering identified subgroups of AYAs showing a unique pattern of cognitive functioning in the long-term. Results Participants (n=93; mean age 20y 1mo [standard deviation {SD} 4y 6mo]; 36% male) were followed for 7 years (SD 2y 4mo), of whom 65% had undergone resective epilepsy surgery. Two subgroups with unique patterns of cognitive functioning were identified, which could be broadly categorized as 'impaired cognition' (45% of the sample) and 'average cognition' (55% of the sample); the mean z-score across cognitive measures at follow-up was -1.86 (SD 0.62) and -0.23 (SD 0.54) respectively. Surgical and non-surgical patients were similar with respect to seizure control and their long-term cognitive profile. AYAs in the average cognition cluster were more likely to have better cognition at baseline, an older age at epilepsy onset, and better seizure control at follow-up. Interpretation The underlying abnormal neural substrate and seizure control were largely associated with long-term outcomes across cognitive domains.

PURPOSE To identify factors that may influence physician participation in tumor profiling studies and to assess the routine use of tumor profiling in clinical practice. METHODS Physicians in the National Cancer Institute–Molecular Analysis for Therapy Choice (NCI-MATCH) were invited to participate in an electronic survey consisting of 73 questions related to participation in genomic profiling studies, tumor profiling practices and education during usual patient care, and physician background and practice characteristics. RESULTS The survey response rate was 8.9% (171 surveys returned of 1,931 sent). A majority of respondents practiced in academic medical centers (AMCs). Participation in NCI-MATCH increased workload and cost but resulted in increased professional satisfaction, confidence in treatment recommendation, and subsequent use of tumor profiling. Barriers to patient participation included length of wait time for results and lack of a therapeutic option from the testing. Physicians who worked in AMCs reported a higher use of tumor profiling than did those who worked in non-AMC settings (43% v 18%; P = .0009). Access to a molecular tumor board was perceived as valuable by 56%. The study identified a need for educational materials to guide both physicians and patients in the field of genomic profiling. CONCLUSION Physicians who participate in NCI-MATCH perceive value to patient treatment that outweighs the additional effort required; survey results help identify barriers that may limit participation. The current findings have implications for the design of future genomic and other profiling studies.

Quality of life (QOL) is recognized as a key outcome of chronic health conditions and is increasingly used and recommended for clinical care and clinical trials. Neurocognitive developmental disorders and disabilities (NDD) are characterized by impairments or comorbidities in multiple areas of function, and, unsurprisingly, youth with NDD and their families have poorer QOL relative to their peers. The impact of NDD goes beyond the characteristic symptoms of the illness, and youth with NDD face numerous comorbidities and psychosocial problems that may have a large impact on QOL. In this chapter, first, we discuss the varying approaches and methodological considerations associated with the measurement of QOL and the implications of using "generic," "disease-specific," and proxy-reported measures of QOL. Second, we review the literature evaluating the QOL of youth with various NDD relative to healthy controls and factors associated with outcomes. Last, we conclude with a review of the literature outlining the importance of family environment, the compromised QOL of parents of youth with NDD, and the needs of parents. Evaluation of QOL is an important and recommended component of comprehensive care and clinical trials.

Objective To examine longitudinal changes and predictors of depression and anxiety 2 years following resective epilepsy surgery, compared to no surgery, in children with drug-resistant epilepsy (DRE). Method This multicenter cohort study involved 128 children and adolescents with DRE (48 surgical, 80 nonsurgical; 8–18 years) who completed self-report measures of depression and anxiety at baseline and follow-up (6-month, 1-year, 2-year). Child demographic (age, sex, IQ) and seizure (age at onset, duration, frequency, site and side) variables were collected. Results Linear mixed-effects models controlling for age at enrolment found a time by treatment by seizure outcome interaction for depression. A negative linear trend across time (reduction in symptoms) was found for surgical patients, irrespective of seizure outcome. In contrast, the linear trend differed depending on seizure outcome in nonsurgical patients; a negative trend was found for those with continued seizures, whereas a positive trend (increase in symptoms) was found for those who achieved seizure freedom. Only a main effect of time was found for anxiety indicating a reduction in symptoms across patient groups. Multivariate regressions failed to find baseline predictors of depression or anxiety at 2-year follow-up in surgical patients. Older age, not baseline anxiety or depression, predicted greater symptoms of anxiety and depression at 2-year follow-up in nonsurgical patients. Conclusion Children with DRE reported improvement in anxiety and depression, irrespective of whether they achieve seizure control, across the 2 years following surgery. In contrast, children with DRE who did not undergo surgery, but achieved seizure freedom, reported worsening of depressive symptoms, which may indicate difficulty adjusting to life without seizures and highlight the potential need for ongoing medical and psychosocial follow-up and support.

Objective This study estimated trajectories of health-related quality of life (HRQOL) over a 10-year period among children newly diagnosed with epilepsy. We also modeled the characteristics of children, parents, and families associated with each identified trajectory. Methods Data came from the HERQULES (Health-Related Quality of Life in Children With Epilepsy Study), a Canada-wide prospective cohort study of children (aged 4-12 years) with newly diagnosed epilepsy. Parents reported on their children's HRQOL at diagnosis, and at 0.5-, 1-, 2-, 8-, and 10-year follow-ups using the Quality of Life in Childhood Epilepsy Questionnaire-55. Trajectories of HRQOL were identified using latent class growth models. Characteristics of children, parents, and families at the time of diagnosis that were associated with each trajectory were identified using multinomial logistic regression. Results A total of 367 children were included. Four unique HRQOL trajectories were identified; 11% of the cohort was characterized by low and stable scores, 18% by intermediate and stable scores, 35% by intermediate scores that increased then plateaued, and 43% by high scores that increased then plateaued. Absence of comorbidities, less severe epilepsy, and better family environment (greater satisfaction with family relationships and fewer family demands) at the time of diagnosis were associated with better long-term HRQOL trajectories. Although the analyses used estimates for missing values and accounted for any nonrandom attrition, the proportion of children with poorer HRQOL trajectories may be underestimated. Significance Children with new onset epilepsy are heterogenous and follow unique HRQOL trajectories over the long term. Overall, HRQOL improves for the majority in the first 2 years after diagnosis, with these improvements sustained over the long term.

OBJECTIVE To evaluate longitudinal changes in caregiver depression, anxiety, and family relationships following resective surgery for pediatric drug-resistant epilepsy (DRE). METHODS This multicenter cohort study involved 177 caregivers of children with DRE aged 4-18 years (63 surgical and 114 nonsurgical). Caregivers completed measures of depression (Quick Inventory of Depressive Symptomatology), anxiety (Generalized Anxiety Disorder 7-item scale), and satisfaction with family relationships (Family Adaptability, Partnership, Growth, Affective, and Resolve scale) at baseline, 6 months, and 1 year. Additional data collected at baseline included child, caregiver, and family sociodemographic and clinical factors as well as family environment (demands and resources). RESULTS At 1 year, 64% and 27% of surgical and nonsurgical patients were seizure-free, respectively. Linear mixed-effects models found a reduction in caregiver depression (b = -0.85, P = .004) and anxiety (b = -1.09, P = .003), but not family satisfaction (b = 0.18, P = .31) over time. There was no effect of treatment. When seizure outcome was added to the model, seizure freedom was associated with fewer depressive symptoms (b = -1.15, P = .005) and greater family satisfaction (b = 0.65, P = .006), but not anxiety (b = -0.41, P = .42). A greater proportion of caregivers of patients who achieved seizure freedom (32%) versus continued seizures (18%) reported clinically meaningful improvement in depression at 1 year (P = .03). Lower baseline depression (β = 0.42, P

These NCCN Guidelines Insights highlight the updated recommendations for use of multigene assays to guide decisions on adjuvant systemic chemotherapy therapy for women with hormone receptor–positive, HER2-negative early-stage invasive breast cancer. This report summarizes these updates and discusses the rationale behind them.

Objective To prospectively delineate self-reported health-related quality of life (HRQOL) of adolescents and young adults (AYAs) 8 and 10 years after an epilepsy diagnosis and evaluate the degree of AYA-parent agreement in ratings of AYA's HRQOL. Methods Data came from the Health-Related Quality of Life in Children with Epilepsy Study (HERQULES), a 10-year longitudinal study of children, aged 4-12 years, with newly diagnosed epilepsy. Epilepsy-specific HRQOL was self-reported by AYA 8 and 10 years after diagnosis and by parents at multiple time points throughout the 10-year follow-up. Measurers of HRQOL over time were analyzed using a linear mixed-effect model approach. AYA-parent agreement was evaluated using intraclass correlation coefficient (ICC) and Bland-Altman plots. Results A total of 165 AYAs participated at long-term follow-up. There was considerable heterogeneity among AYA's HRQOL, and as a group, there was no significant change in HRQOL from the 8- to 10-year follow-up. Household income at the time of diagnosis, seizure control at follow-up, and a history of emotional problems (anxiety/depression) were independent predictors of HRQOL at follow-up. AYA-parent agreement on AYA's HRQOL was moderate (ICC 0.62, 95% CI 0.51-0.71), although considerable differences were observed at the individual level. AYA-parent agreement varied with AYA's and parent's age, seizure control, and family environment. Significance In the long-term after a diagnosis of epilepsy, AYAs report stable HRQOL over time at the group level, although notable individual differences exist. Seizure control, anxiety/depression, and family environment meaningfully impact AYA's long-term HRQOL. AYA and parent reports on HRQOL are similar at the group level, although they cannot be used interchangeably, given the large individual differences observed.

BackgroundCombination antiretroviral therapy (cART) during pregnancy prevents vertical transmission, but many antiretrovirals cross the placenta and several can affect mitochondria. Exposure to maternal human immunodeficiency virus (HIV) and/or cART could have long-term effects on children who are HIV exposed and uninfected (CHEU). Our objective was to compare blood mitochondrial DNA (mtDNA) content in CHEU and children who are HIV unexposed and uninfected (CHUU), at birth and in early life.MethodsWhole-blood mtDNA content at birth and in early life (age 0–3 years) was compared cross-sectionally between CHEU and CHUU. Longitudinal changes in mtDNA content among CHEU was also evaluated.ResultsAt birth, CHEU status and younger gestational age were associated with higher mtDNA content. These remained independently associated with mtDNA content in multivariable analyses, whether considering all infants, or only those born at term. Longitudinally, CHEU mtDNA levels remained unchanged during the first 6 months of life, and gradually declined thereafter. A separate age- and sex-matched cross-sectional analysis (in 214 CHEU and 214 CHUU) illustrates that the difference in mtDNA between the groups remains detectable throughout the first 3 years of life.ConclusionThe persistently elevated blood mtDNA content observed among CHEU represents a long-term effect, possibly resulting from in utero stresses related to maternal HIV and/or cART. The clinical impact of altered mtDNA levels is unclear.

Neurodevelopmental difficulties emerge in very preterm born children (, Graphical Abstract Graphical Abstract

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non-muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non-muscle-invasive bladder cancer in the event of a bacillus Calmette-Guerin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.

12094 Background: The Functional Assessment of Cancer Therapy patient-reported outcomes (PRO) item GP5 (“I am bothered by side effects of treatment”) estimates treatment tolerability. We aimed to extend our previous finding that GP5 predicts early aromatase inhibitor (AI) discontinuation (E1Z03, 96% White) in the racially diverse E1Z11 trial cohort. Methods: E1Z11 was coordinated by the ECOG-ACRIN NCI Community Oncology Research Program (NCORP) Research Base. Postmenopausal women initiating anastrozole per clinical care for ER+ stage I-III breast cancer with a pain score 0-3/10 and no rheumatologic comorbidities were eligible. Accrual of a racially diverse cohort of 1,000 women, including Black and Asian women, was planned. GP5 was administered prior to initiating anastrozole (trial baseline) and at 3, 6, 9 and 12 months. GP5 was scored on a 5-point Likert scale from 0 (not at all) to 4 (very much) and dichotomized as no/little treatment bother (0/1) or moderate/high treatment bother (2-4), consistent with previous analyses. A univariate Cox proportional hazards model estimated baseline GP5’s association with treatment duration via hazard ratio (HR). Early treatment discontinuation status was defined as treatment duration < 12 months with discontinuation not attributed to disease progression or death (n = 4), consistent with previous analyses. Results: 1,046 women enrolled from 6/2013-10/2018 (640 White, 201 Black, 205 Asian), including 590 (56%) from NCORP Community or Minority/Underserved Sites. Approximately 10% (100/987 with GP5 data) reported moderate/high treatment bother prior to initiating anastrozole. Anastrozole discontinuation rate at 1-year was 26.2% overall; it was lower among women with no/little treatment bother (25.7%, GP5 = 0-1) compared to moderate/high treatment bother prior to initiating anastrozole (34.7%, GP5 = 2-4; HR = 1.50, 95% confidence interval [CI]:1.04-2.15, p = 0.027). Subgroup analyses by racial cohort showed a similar predictive effect of GP5 in the White (n = 606, HR = 1.76, 95% CI: 1.12-2.77, p = 0.014) and Black (n = 184, HR = 1.85, 95% CI: 0.92-3.71, p = 0.079) cohorts, but not in the Asian cohort (n = 197, HR = 0.40, 95% CI: 0.10-1.62, p = 0.20). Conclusions: Moderate/high treatment bother prior to starting anastrozole was observed in 10% of patients and associated with a higher risk of early discontinuation, except in Asian patients. Our findings support the presence of a treatment tolerability threshold which can be compromised by pre-treatment burden. Treatment tolerability may also be influenced by cultural and genetic factors, which will be explored in further analysis of genetic and PRO data. Clinical trial information: NCT01824836.

521 Background: Clinical trials provide the foundation for evidence-based practices, yet trial participants are often not representative of all patients. Historically, clinical trials involved adding novel agents to standard of care to improve survival. There has been a shift to an individualized approach with testing less intense treatment, yet vulnerable patient groups are at risk for underrepresentation. Little is known about physician perspectives on implementing less intense treatment approaches for patients who are not represented in sufficient number to draw conclusions on subpopulations. Methods: Open-ended, individual qualitative interviews with medical oncologists from different cancer centers exploring their perspectives on trials that test less intense treatment for patients with cancer. Interviews were audio-recorded and transcribed. Four independent coders utilized a content analysis approach to analyze transcripts using NVivo. Major themes and exemplary quotes were extracted. Results: Of the 39 participating physicians, 61.5% felt comfortable extrapolating, 30.8% were hesitant, and 7.7% would not feel comfortable extrapolating trial outcomes to underrepresented populations. One physician noted, “We've been extrapolating for as long as I can remember and certainly that I've been in practice; so we do need to do better there, but extrapolation is only natural with what we have.” Facilitators of comfort included sentiment that “biology is biology”, such that the cancer characteristics were what mattered; the strength of the evidence from the trial overall; inclusion of subset analysis on underrepresented populations; and prior experience making decisions with limited data. Barriers to extrapolation included the potential harm over the patient’s lifetime; concerns about groups that had minimal participants; application specifically to younger patients; and extending findings to racially and ethnically diverse populations. Oncologists highlighted the need for shared decision-making when applying study results to underrepresented populations. They also expressed concerns about study findings being applied to patients who would have been ineligible in the original trials. Universally, broader inclusion in trials testing lowering chemotherapy is desired. Conclusions: The majority (92%) of physicians report that they would extrapolate clinical trial results to patients poorly represented in de-escalation trials, while expressing concerns about applicability to specific subpopulations based on tumor characteristics (e.g. stage, biology) and patient demographics (e.g. age, race). Further work is needed to increase clinical trial representation of diverse populations to safely and effectively optimize treatment for patients with cancer.

Purpose To provide evidence-based consensus recommendations on choice of end points for clinical trials in metastatic breast cancer, with a focus on biologic subtype and line of therapy. Methods The National Cancer Institute Breast Cancer Steering Committee convened a working group of breast medical oncologists, patient advocates, biostatisticians, and liaisons from the Food and Drug Administration to conduct a detailed curated systematic review of the literature, including original reports, reviews, and meta-analyses, to determine the current landscape of therapeutic options, recent clinical trial data, and natural history of four biologic subtypes of breast cancer. Ongoing clinical trials for metastatic breast cancer in each subtype also were reviewed from ClinicalTrials.gov for planned primary end points. External input was obtained from the pharmaceutic/biotechnology industry, real-world clinical data specialists, experts in quality of life and patient-reported outcomes, and combined metrics for assessing magnitude of clinical benefit. Results The literature search yielded 146 publications to inform the recommendations from the working group. Conclusion Recommendations for appropriate end points for metastatic breast cancer clinical trials focus on biologic subtype and line of therapy and the magnitude of absolute and relative gains that would represent meaningful clinical benefit.

The current study examined pre- and postoperative health-related quality of life (HRQL) across children with and without low intellectual ability. We also aimed to clarify the literature on postsurgical change by assessing domain-specific HRQL pre- and postoperatively in children with drug-resistant epilepsy.All patients (n=111) underwent resective epilepsy surgery between 1996 and 2016 at the Hospital for Sick Children in Toronto, comparing baseline and 1-year follow-up HRQL with the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-76). At the group-level, postsurgical change in HRQL was examined through linear mixed-effects modeling. Clinically important change in HRQL at the individual level was quantified using a standard error of measurement (SEM)-based criterion, and estimates were stratified by intellectual ability.Children with epilepsy and low intellectual ability had lower overall HRQL compared with those with normal intelligence (b=-10.45, SE=4.89, p=.035). No differences in change in HRQL related to intellectual level were found. In the broader sample, significant postoperative improvements were found for HRQL related to physical activity (b=8.28, SE=1.79, p.001), social activity (b=15.81, SE=2.76, p.001), and behavior (b=4.34, SE=1.35, p=.001). Postoperative improvements in physical and social HRQL were associated with better seizure control (p=.011). Conversely, cognitive and emotional domains of HRQL did not improve one year postoperatively, even in the presence of improved seizure control.Results suggest that children with low intellectual ability can expect to achieve similar improvements in HRQL after epilepsy surgery compared with those with normal intelligence. Further, while overall HRQL is shown to improve in children following epilepsy surgery, domain-specific change is nuanced and has important implications for health practitioners aiming to monitor treatment progress of patients.

This study examined functional changes longitudinally over 2 years in neural correlates associated with working memory in youth with and without autism spectrum disorder, and the impact of increasing cognitive load. We used functional magnetic resonance imaging and a visuo-spatial 1-back task with four levels of difficulty. A total of 14 children with autism spectrum disorder and 15 typically developing children (ages 7–13) were included at baseline and followed up approximately 2 years later. Despite similar task performance between groups, differences were evident in the developmental trajectories of neural responses. Typically developing children showed greater load-dependent activation which intensified over time in the frontal, parietal and occipital lobes and the right fusiform gyrus, compared to those with autism spectrum disorder. Children with autism spectrum disorder showed minimal age-related changes in load-dependent activation, but greater longitudinal load-dependent deactivation in default mode network compared to typically developing children. Results suggest inadequate modulation of neural activity with increasing cognitive demands in children with autism spectrum disorder, which does not mature into adolescence, unlike their typically developing peers. Diminished ability for children with autism spectrum disorder to modulate neural activity during this period of maturation suggests that they may be more vulnerable to the increasing complexity of social and academic demands as they progress through adolescence than their peers.

Children born very preterm (VPT) at less than 32 weeks' gestational age (GA) are prone to disrupted white matter maturation and impaired cognitive development. The aims of the present study were to identify differences in white matter microstructure and connectivity of children born VPT compared to term-born children, as well as relations between white matter measures with cognitive outcomes and early brain injury. Diffusion images and T1-weighted anatomical MR images were acquired along with developmental assessments in 31 VPT children (mean GA: 28.76 weeks) and 28 term-born children at 4 years of age. FSL's tract-based spatial statistics was used to create a cohort-specific template and mean fractional anisotropy (FA) skeleton that was applied to each child's DTI data. Whole brain deterministic tractography was performed and graph theoretical measures of connectivity were calculated based on the number of streamlines between cortical and subcortical nodes derived from the Desikan-Killiany atlas. Between-group analyses included FSL Randomise for voxel-wise statistics and permutation testing for connectivity analyses. Within-group analyses between FA values and graph measures with IQ, language and visual-motor scores as well as history of white matter injury (WMI) and germinal matrix/intraventricular haemorrhage (GMH/IVH) were performed. In the children born VPT, FA values within major white matter tracts were reduced compared to term-born children. Reduced measures of local strength, clustering coefficient, local and global efficiency were present in the children born VPT within nodes in the lateral frontal, middle and superior temporal, cingulate, precuneus and lateral occipital regions. Within-group analyses revealed associations in term-born children between FA, Verbal IQ, Performance IQ and Full scale IQ within regions of the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, forceps minor and forceps major. No associations with outcome were found in the VPT group. Global efficiency was reduced in the children born VPT with a history of WMI and GMH/IVH. These findings are evidence for under-developed and less connected white matter in children born VPT, contributing to our understanding of white matter development within this population.

Assessment of naming in children has been hampered by the use of tests that were developed, either to assess naming in adults or to assess related verbal functions in children. We developed comparable visual naming test (VNT) and auditory description naming (ANT) specifically for children. We collected normative data, not only for accuracy, typically the sole performance measure, but also for response time (RT) and reliance on phonemic cuing. The normative sample consisted of 200 typically developing children, ages 6-15, with 40 children per 2-year age group (6-7, 8-9, 10-11, 12-13, and 14-15). Children were tested individually by a trained examiner. Based on item analysis, naming tests were finalized at 36 items for ages 8-15 and 28 items for ages 6-7. Age-stratified normative data are provided for accuracy, mean RT, tip-of-the-tongues (i.e., delayed but accurate responses plus items named following phonemic cueing), and a summary score, which incorporates all performance measures. Internal and test-retest reliability coefficients for both tests were reasonable. Accuracy scores were high across age groups, indicating that item names were within the mental lexicon of most typically developing children. By contrast, time and cue-based scores improved with age, reflecting greater efficiency in word retrieval with development. These complementary auditory naming and visual naming tests for children address a longstanding clinical need, improving upon the current standard with respect to the sensitivity of performance measures and the addition of an auditory verbal component to the assessment of naming in children.

Very preterm (VPT) birth (

To determine the extent to which specific neuropsychological measures are in common use around the world for the assessment of children who are candidates for epilepsy surgery. As part of the work of the International League Against Epilepsy Pediatric Surgical Task Force, a survey was developed and distributed online. The survey consisted of questions related to demographics, training experience, general practice, and specific measures used and at what frequency. Seventy-eight clinicians with an average of 13.5 years of experience from 19 countries responded to the survey; 69% were English-speaking. Pre- and post-neuropsychological evaluations were conducted with a majority of children undergoing surgical resection for epilepsy. There was high consistency (>90%) among the domains evaluated, while consistency rate among specific measures was more variable (range: 0-100%). Consistency rates were also lower among respondents in non-English-speaking countries. For English-speaking respondents, at least one measure within each domain was used by a majority (>75%) of clinicians; 19 specific measures met this criterion. There is consensus of measures used in neuropsychological studies of pediatric epilepsy patients which provides a basis for determining which measures to include in establishing a collaborative data repository to study surgical outcomes of pediatric epilepsy. Challenges include selecting measures that promote collaboration with centers in non-English-speaking countries and providing data from children under age 5.

Little is known about the neurodevelopmental outcomes of children older than 3 years of age born to HIV infected mother but who are HIV-uninfected (HEU), and who have been exposed in utero and early in life to HIV and to antiretroviral medications (ARVs). We conducted a longitudinal study of cognitive, visuomotor and adaptive function of HEU children, who were assessed at two ages, 3.5 and 5.5 years. Sixty-four children (33 female) were assessed. In comparison with population norms for their age, at 3.5 years of age they had scores significantly below age expectations on aspects of adaptive behavior, but at age 5.5 years, their scores did not significantly diverge from the population norms on any of the measures. Verbal intelligence was lower at age 5.5 than at age 3.5 years, although there were also improvements in some features of adaptive behavior. Exposure to PI-based ARVs (compared to NNRTIs) was associated with higher Performance IQ, visuomotor and communication scores at age 5.5 years. Birth, early growth, and sociodemographic variables were predictive of outcomes. This study is important in tracking the trajectory of neurocognitive development across the pre-school and early school age years. The findings suggest that the full impact of early ARV exposure may not be evident until a considerable period of development has occurred. The results raise the possibility of negative effects of early ARV exposure on neurodevelopment that emerge over time, and reiterate the importance of sociodemographic and early health variables for optimal development.

These NCCN Guidelines Insights highlight the important updates/changes to the surgical axillary staging, radiation therapy, and systemic therapy recommendations for hormone receptor-positive disease in the 1.2017 version of the NCCN Guidelines for Breast Cancer. This report summarizes these updates and discusses the rationale behind them. Updates on new drug approvals, not available at press time, can be found in the most recent version of these guidelines at NCCN.org.

Objective A vast proportion of children with epilepsy exhibit memory impairments. Although numerous studies have examined memory performance following pediatric resective epilepsy surgery, little is known about the memory outcomes following hemispherectomy. The few studies that report on memory performance typically include restricted measures, consist of case reports, or do not report on preoperative performance. Given the current limitations, the aim of this study was to delineate pre- and postoperative memory functioning in youth who underwent a hemispherectomy. Method Participants included patients who had undergone a hemispherectomy at the Hospital for Sick Children, between 1999 and 2016. Standardized neuropsychological assessments of verbal (digit span, word list recall, word pair recall, stories) and visual (faces, dot locations) memory abilities prior to and after surgery were reviewed. A Wilcoxon signed rank test and effect sizes was completed to compare patients' memory performance to population norms and to assess pre- to postoperative difference scores. Results Thirteen participants were included in the study: five patients completed preoperative assessments only and eight patients completed pre- and postoperative assessments. Preoperatively, patients performed substantially worse relative to population norms as indicated by large effect sizes (r: 0.5–0.9). Postoperatively, effect sizes were large for the majority of the memory tests, demonstrating considerable differences in patients' memory scores over time. When clinically meaningful changes were examined, stable performance was evident on 63% of the memory tasks. Conclusion Overall, the results highlight that youth who are eligible for hemispherectomy demonstrate profound memory deficits prior to surgery. In addition, undergoing hemispherectomy was not necessarily associated with declined memory performance, with the majority of patients showing stable scores.

PURPOSE: Patient-reported outcome measures (PROMs) that assess how patients feel and function have potential for evaluating quality of care. Stakeholder recommendations for PRO-based performance measures (PMs) were elicited, and feasibility testing was conducted at six cancer centers. METHODS: Interviews were conducted with 124 stakeholders to determine priority symptoms and risk adjustment variables for PRO-PMs and perceived acceptability. Stakeholders included patients and advocates, caregivers, clinicians, administrators, and thought leaders. Feasibility testing was conducted in six cancer centers. Patients completed PROMs at home 5-15 days into a chemotherapy cycle. Feasibility was operationalized as ≥ 75% completed PROMs and ≥ 75% patient acceptability. RESULTS: Stakeholder priority PRO-PMs for systemic therapy were GI symptoms (diarrhea, constipation, nausea, vomiting), depression/anxiety, pain, insomnia, fatigue, dyspnea, physical function, and neuropathy. Recommended risk adjusters included demographics, insurance type, cancer type, comorbidities, emetic risk, and difficulty paying bills. In feasibility testing, 653 patients enrolled (approximately 110 per site), and 607 (93%) completed PROMs, which indicated high feasibility for home collection. The majority of patients (470 of 607; 77%) completed PROMs without a reminder call, and 137 (23%) of 607 completed them after a reminder call. Most patients (72%) completed PROMs through web, 17% paper, or 2% interactive voice response (automated call that verbally asked patient questions). For acceptability, > 95% of patients found PROM items to be easy to understand and complete. CONCLUSION: Clinicians, patients, and other stakeholders agree that PMs that are based on how patients feel and function would be an important addition to quality measurement. This study also shows that PRO-PMs can be feasibly captured at home during systemic therapy and are acceptable to patients. PRO-PMs may add value to the portfolio of PMs as oncology transitions from fee-for-service payment models to performance-based care that emphasizes outcome measures.

PURPOSE To update the ASCO guideline on the recommended prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer survivors. METHODS An Expert Panel conducted targeted systematic literature reviews to identify new studies. RESULTS The search strategy identified 257 new references, which led to a full-text review of 87 manuscripts. A total of 3 systematic reviews, 2 with meta-analyses, and 28 primary trials for prevention of CIPN in addition to 14 primary trials related to treatment of established CIPN, are included in this update. RECOMMENDATIONS The identified data reconfirmed that no agents are recommended for the prevention of CIPN. The use of acetyl-l-carnitine for the prevention of CIPN in patients with cancer should be discouraged. Furthermore, clinicians should assess the appropriateness of dose delaying, dose reduction, substitutions, or stopping chemotherapy in patients who develop intolerable neuropathy and/or functional impairment. Duloxetine is the only agent that has appropriate evidence to support its use for patients with established painful CIPN. Nonetheless, the amount of benefit from duloxetine is limited. Additional information is available at www.asco.org/survivorship-guidelines .

Quality of life (QOL) is recognized as a key outcome of chronic health conditions and is increasingly used and recommended for clinical care and clinical trials. Neurocognitive developmental disorders and disabilities (NDD) are characterized by impairments or comorbidities in multiple areas of function, and, unsurprisingly, youth with NDD and their families have poorer QOL relative to their peers. The impact of NDD goes beyond the characteristic symptoms of the illness, and youth with NDD face numerous comorbidities and psychosocial problems that may have a large impact on QOL. In this chapter, first, we discuss the varying approaches and methodological considerations associated with the measurement of QOL and the implications of using "generic," "disease-specific," and proxy-reported measures of QOL. Second, we review the literature evaluating the QOL of youth with various NDD relative to healthy controls and factors associated with outcomes. Last, we conclude with a review of the literature outlining the importance of family environment, the compromised QOL of parents of youth with NDD, and the needs of parents. Evaluation of QOL is an important and recommended component of comprehensive care and clinical trials.

Objective The objective of the study was to validate the parent-proxy reported Quality of Life in Childhood Epilepsy Questionnaire (QOLCE) in a sample of young adults with a history of childhood-onset epilepsy, allowing for the utilization of a consistent informant (the parent) across the youths' stages of development. The 55-item (QOLCE-55) and 16-item versions (QOLCE-16) were evaluated. Methods Data came from 134 young adults (aged 18.0 to 28.5 years) with childhood-onset epilepsy, recruited through community and tertiary care centers across Canada. Confirmatory factor analysis (CFA) was used to assess the higher-order factor structure of the QOLCE. Cronbach's alpha was used to evaluate internal consistency. Convergent validity was assessed by intraclass correlation coefficients (ICC) with the youth self-reported Quality of Life in Epilepsy Questionnaire (QOLIE-31-P). Results The higher-order factor structure of the QOLCE-55 and QOLCE-16 demonstrated adequate fit: QOLCE-55 comparative fit index (CFI) = 0.968, Tucker–Lewis index (TLI) = 0.966; and root mean square of approximation (RMSEA) = 0.061; QOLCE-16 CFI = 0.966, TFI = 0.959, RMSEA = 0.141. Higher-order factor loadings were strong, ranging from 0.71 to 0.90. Internal consistency was excellent for the total score (αQOLCE-55 = 0.97; αQOLCE-16 = 0.93) and good-excellent for each subscale (α > 78). Convergent validity was moderate to good for the total score (ICC > 0.72) and each subscale (ICC > 0.51). Significance These findings provide support for the use of the QOLCE-55 and QOLCE-16 among young adults with a history of childhood-onset epilepsy. Utilizing a consistent measure and informant across the stages of development is essential to reliably evaluate change over time.

To determine whether epilepsy surgery improved health-related quality of life (HRQoL) and whether seizure freedom after surgery mediated the improvement in HRQoL.This multicenter cohort study compared HRQoL after epilepsy surgery to pharmacological management in children with drug-resistant epilepsy (DRE). HRQoL was measured using the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire at baseline and 1-year follow-up. The mediator between treatment type and HRQoL was seizure freedom.Two hundred and thirty-seven patients were recruited (surgery group: n=147 [92 males, 45 females]; pharmacological group: n=90 [53 males, 37 females]). Mean age at seizure onset was 6 years (SD 4y 4mo) in the surgical group and 6 years 1 month (SD 4y) in the pharmacological group. The odds ratio of seizure freedom was higher for the surgery versus pharmacological group (β=4.24 [95% confidence interval {CI}: 2.26-7.93], p0.001). Surgery had no direct effect on total QOLCE score at 1-year (β=0.24 [95% CI -2.04 to 2.51], p=0.839) compared to pharmacological management, but had an indirect effect on total QOLCE that was mediated by seizure freedom (β=0.92 [95% CI 0.19-1.65], p=0.013), adjusting for baseline total QOLCE score. Surgery had a direct effect on improving social function (p=0.043), and an indirect effect on improving physical function (p=0.016), cognition (p=0.042), social function (p=0.012) and behavior (p=0.032), mediated by seizure freedom.Greater seizure freedom achieved through epilepsy surgery mediated the improvement in HRQoL compared to pharmacological management in children with DRE.Seizure freedom is higher after pediatric epilepsy surgery compared to pharmacologically managed epilepsy. Surgery indirectly improves health-related quality of life (HRQoL) mediated by seizure freedom compared to pharmacological management. Surgery has a direct effect on improving social function relative to pharmacological management. Baseline HRQoL was an important predictor of HRQoL after treatment.LA AUSENCIA DE CRISES EPILÉPTICAS EN NIÑOS MEJORA LA CALIDAD DE VIDA RELACIONADA CON LA SALUD DESPUÉS DE LA CIRUGÍA DE EPILEPSIA: OBJETIVO: Determinar si la cirugía de epilepsia mejora la calidad de vida relacionada con la salud (HRQoL) y si la ausencia de crises epilépticas después de la cirugía intervino en la mejora.Estudio de cohorte, multicéntrico que evaluó la HRQoL después de la cirugía de epilepsia comparándolo con el manejo farmacológico, en niños con epilepsia farmacorresistente (DRE). La HRQoL se midió utilizando el cuestionario de calidad de vida en la infancia (QOLCE) al inicio y después de un año de seguimiento. El mediador entre el tipo de tratamiento y HRQoL fue la ausencia de crises epilépticas.Se reclutaron 237 pacientes (grupo de cirugía: n 147 [92 varones, 45 mujeres]; grupo farmacológico: n 90 [53 varones, 37 mujeres]). La edad promedio al inicio de las crisis epilépticas fue de 6 años (DE 4 años 4 meses) en el grupo quirúrgico y 6 años 1 mes (DE 4 años) en el grupo farmacológico. La relación de probabilidad de la ausencia de crises epilépticas fue mayor para el grupo de cirugía frente a farmacológico (β = 4,24 [intervalo de confianza (IC) 95 %: 2.26-7.93], p0.001). La cirugía no tiene ningún efecto directo sobre la puntuación total de QOLCE a 1 año (β = 0,24 [IC del 95% -2,04 a 2,51], p=0,839) en comparación con el tratamiento farmacológico, pero tiene un efecto indirecto en el QOLCE total que fue mediado por la ausencia de crises epilépticas (β = 0,92 [IC del 95% 0,19-1,65], p=0,013), ajustando la puntuación total de QOLCE. La cirugía tuvo un efecto directo en la mejora de la función social (p=0.043), y un efecto indirecto en la mejora de la función física (p=0.016), la cognición (p=0,042), la función social (p=0.012) y el comportamiento (p=0.032), mediado por la ausencia de crises epilépticas.En este estudio encontramos que en niños con DRE la ausencia mas significativa de crises epilépticas, lograda a través de la cirugía de epilepsia, mediaba una mejor HRQoL en comparación con el manejo farmacológico.FICAR SEM CRISES EPILÉPTICAS MELHORA A QUALIDADE DE VIDA RELACIONADA À SAÚDE APÓS CIRURGIA PARA EPILEPSIA EM CRIANÇAS: OBJETIVO: Determinar se a cirurgia para epilepsia melhora a qualidade de vida relacionada à saude (QVRS) e se ficar sem crises epilépticas após a cirurgia media a melhora na QVRS. MÉTODO: Este estudo de coorte multicêntrico comparou a QVRS após cirurgia para epilepsia ao manejo farmacológico em criancas com epilepsia resistente a drogas (ERD). A QVRS foi medida usando o questionário Qualidade de Vida na Epilepsia Infantil (QVEI) na linha de base e no acompanhamento após 1 ano. O mediador entre o tipo de tratamento e a QVRS foi estar sem crises epilépticas. RESULTADOS: Duzentos e trinta e sete pacientes foram recrutados (grupo cirurgia: n=147 [92 do sexo masculino, 45 do sexo feminino]; grupo farmacológico: n=90 [53 do sexo masculino, 37 do sexo feminino]). A média de idade no início das crises foi 6 anos (DP 4a 4m) no grupo cirúrgico e 6 anos e 1 mês (DP 4a) no grupo farmacológico. A taxa de risco de estar sem crises foi maior no grupo cirurgia versus farmacológico (β=4,24 [intervalo de confiança a 95% {IC}: 2,26-7,93], p0,001). A cirurgia não teve efeito direto no QVEI total após 1 ano (β=0,24 [IC 95% -2,04 a 2,51], p=0,839) comparada ao manejo farmacológico, mas teve efeito indireto no QVEI total que foi medido pelo fato de estar livre de crises (β=0,92 [IC 95% 0,19-1,65], p=0,013), ajustando para o escore total QVEI na linha de base. A cirurgia teve efeito direto na melhora da função social (p=0,043), e efeito indireto na melhora da função física (p=0,016), cognição (p=0,042), função social (p=0.012) comportamento (p=0,032), mediada pelo fato de estar sem crises. INTERPRETAÇÃO: A maior chance de ficar sem crises, atingida por meio da cirurgia, mediou a melhora na QVRS em comparação com o manejo farmacológico em crianças com ERD.

BACKGROUND: While there is increased attention to designing and explaining clinical trials in ways that are clinically meaningful for patients, there is limited information on patient preferences, understanding and perceptions of this content. METHODS: Using maximum difference scaling (MaxDiff) methodology, we developed a survey assessing understanding of 19 clinical terms and perceived importance of nine endpoint surrogate phrases employed in clinical trials and consent forms. The survey was administered electronically to individuals with metastatic breast cancer affiliated with the Metastatic Breast Cancer Alliance. Analysis was performed using the “bayesm” package in the R Statistical Package. RESULTS: Among 503 respondents, 77% had a college degree, 70% were diagnosed with metastatic disease ≥2 years prior to survey completion, and 77% had received ≥2 lines of systemic therapy. Less than 35% of respondents reported understanding “fairly well” the terms “symptomatic progression,” “duration of disease control,” “time to treatment cessation,” and “endpoints.” Income level and time since onset of metastatic disease correlated with comprehension. Patients who had received six or more lines of therapy perceived “time until serious side effects” (P

This paper describes 10 core features of a neuropsychological assessment with the aim of helping neurologists understand the unique contribution the evaluation can make within the wider context of diagnostic methods in epilepsy. The possibilities, limitations and cautions associated with the investigation are discussed under the following headings. (1) A neuropsychological assessment is a collaborative investigation. (2) Assessment prior to treatment allows for the accurate assessment of treatment effects. (3) The nature of an underlying lesion and its neurodevelopmental context play an important role in shaping the associated neuropsychological deficit. (4) Cognitive and behavioural impairments result from the essential comorbidities of epilepsy which can be considered as much a disorder of cognition and behaviour as of seizures. (5) Patients' subjective complaints can help us understand objective cognitive impairments and their underlying neuroanatomy, resulting in improved patient care. At other times, patient complaints reflect other factors and require careful interpretation. (6) The results from a neuropsychological assessment can be used to maximize the educational and occupational potentials of people with epilepsy. (7) Not all patients are able to engage with a neuropsychological assessment. (8) There are limitations in assessments conducted in a second language with tests that have been standardized on different populations from that of the patient. (9) Adequate intervals between assessments maximize sensitivity to meaningful change. (10) Patients should be fully informed about the purpose of the assessment and have realistic expectations of the outcome prior to referral.

Introduction The underlying microstructural properties of white matter differences in children born very preterm (, Highlights • Children born VPT have lower FA and higher MD, RD, and ODI in white matter regions. • Higher ODI in the corona radiata was associated with perinatal white matter lesions. • Associations were found between FA and NDI with outcomes in the children born VPT. • NODDI metrics aid interpretation of white matter differences in children born VPT.

To review our experience with the Etomidate speech test (EST) for lateralizing language in children undergoing epilepsy surgery evaluation METHODS: This retrospective study included children (18 years) with drug refractory focal epilepsy undergoing EST for bilateral or poorly reliable language representation on functional MRI. Data for consecutive children who underwent EST between January 2013 to June 2017 were reviewed.Twenty-one children (mean age at EST, 13.1 ± 4.4 years) were studied, with 19-right hemispheric and 20 left hemispheric injections. Six patients had neurological co-morbidities. Duration of ipsilateral EEG slowing was sufficient for speech testing in all children with a single bolus of Etomidate per carotid artery. Language was lateralized to one hemisphere in 17 (80.9%) and bilateral in two cases. EST was unsuccessful in two patients because of diffuse EEG slowing. Contralateral transient frontal EEG slowing was seen in 14 (73.7%) cases. EST was well tolerated in all the patients.The EST was found to be successful and safe in lateralizing language in most of our drug refractory pediatric epilepsy cohort.