Advocate-BREAST: advocates and patients' advice to enhance breast cancer care delivery, patient experience and patient centered research by 2025.

PURPOSE: The aims of the Advocate-BREAST project are to study and improve the breast cancer (BC) patient experience through education and patient-centered research. METHODS: In December 2021, an electronic REDCap survey was circulated to 6,918 BC survivors (stage 0-4) enrolled in the Mayo Clinic Breast Disease Registry. The questionnaire asked about satisfaction with BC care delivery, and education and support receive(d) regarding BC linked concerns. Patients also ranked Quality Improvement (QI) proposals. RESULTS: The survey received 2,437 responses. 18% had Ductal Carcinoma in Situ, 81% had early breast cancer (EBC), i.e. stage 1-3, and 2% had metastatic breast cancer (MBC). Mean age was 64 (SD 11.8), and mean time since diagnosis was 93 months (SD 70.2). 69.3% of patients received all care at Mayo Clinic. The overall experience of care was good (> 90%). The main severe symptoms recalled in year 1 were alopecia, eyebrow/eyelash thinning, hot flashes, sexual dysfunction, and cognitive issues. The main concerns recalled were fear of BC recurrence/spread; loved ones coping; fear of dying, and emotional health. Patients were most dissatisfied with information regarding sexual dysfunction, eyebrow/eyelash thinning, peripheral neuropathy, and on side effects of immunotherapy/targeted therapies. Top ranking QI projects were: i) Lifetime access to concise educational resources; ii) Holistic support programs for MBC and iii) Wellness Programs for EBC and MBC. CONCLUSIONS: Patients with early and advanced BC desire psychological support, concise educational resources, and holistic care. IMPLICATIONS: Focused research and QI initiatives in these areas will improve the BC patient experience.

Neuropsychological and behavioural outcomes in epilepsy involving the insula: A scoping review.

Objective: In patients with epilepsy, the insula has been increasingly recognized as a common site of seizures. There is growing interest in understanding the cognitive and psychological consequences of insular epilepsy to help provide clinical recommendations to support patient's cognitive and psychosocial functioning, and to help identify candidates for epilepsy resective surgery. The aim of this scoping review was to describe the cognitive and behavioural characteristics associated with insular epilepsy in children and adults. Method: A systematic search was completed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis -Extension for Scoping Reviews guidelines. Eligible studies reported on a neuropsychological or behavioural outcome, using standardized or research-based psychological measures, in individuals with insular epilepsy, (i.e. the seizure focus and/or surgical resection included the insula), and a comparison group. After duplicates were removed, 2,423 citations were identified from the search, and 39 studies were included in the scoping review. Results: Across the included studies, intellectual/global cognitive functioning and language were most often evaluated. Lower functioning was found across multiple cognitive and behavioural processes in pediatric and adult patients with insular epilepsy. Following resective surgery involving the insula, behavioural and cognitive outcomes are general stable. Conclusions: The results of this scoping review further neuropsychologists' knowledge of the cognitive and behavioural outcomes of insular seizures prior to and following surgical treatment. These results can aid in counselling patients of the potential cognitive dysfunctions, and aid with treatment planning.

Advocate-BREAST80+: A Comprehensive Patient and Advocate-Led Study to Enhance Breast Cancer Care Delivery and Patient-Centered Research in Women Aged ≥80 Years.

BACKGROUND: There are limited evidence-based data to guide treatment recommendations for breast cancer (BC) patients ≥80 years (P80+). Identifying and addressing unmet needs are critical. AIMS: Advocate-BREAST80+ compared the needs of P80+ vs. patients < 80 years (P80-). METHODS: In 12/2021, a REDCap survey was electronically circulated to 6918 persons enrolled in the Mayo Clinic Breast Disease Registry. The survey asked about concerns and satisfaction with multiple aspects of BC care. RESULTS: Overall, 2437 participants responded (35% response rate); 202 (8.3%) were P80+. P80+ were less likely to undergo local regional and systemic therapies vs. P80- (p < 0.01). Notably, P80+ were significantly less satisfied with information about the short and long-term side effects of BC therapies and managing toxicities. P80+ were also less likely to have participated in a clinical trial (p < 0.001) or to want to do so in the future (p = 0.0001). CONCLUSIONS: Although P80+ experienced less anxiety and symptom-related distress compared with P80-, they were significantly less satisfied with information regarding the side effects of BC therapies and their management. P80+ were significantly less likely to have participated in a clinical trial or be open to considering this option. Future studies should address educational needs pertaining to side effects and barriers to research participation in P80+.

Breast Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Breast cancer is treated with a multidisciplinary approach involving surgical oncology, radiation oncology, and medical oncology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget's disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of systemic therapy (preoperative and adjuvant) options for nonmetastatic breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

Patient-Reported Adverse Events and Early Treatment Discontinuation Among Patients With Multiple Myeloma.

Importance: There is substantial interest in capturing cancer treatment tolerability from the patient's perspective using patient-reported outcomes (PROs). Objective: To examine whether a PRO question, item 5 from the Functional Assessment of Cancer Therapy-General General Physical Wellbeing Scale (GP5), was associated with early treatment discontinuation (ETD) due to adverse events. Design, Setting, and Participants: This prospective survey study was conducted from February to April 2023. Among participants in the ECOG-ACRIN E1A11 trial (a phase 3, parallel design trial conducted between 2013 and 2019), patients with newly diagnosed multiple myeloma were randomized to receive bortezomib (VRd) or carfilzomib (KRd) plus lenalidomide and dexamethasone as induction therapy. The GP5 item was administered at baseline (pretreatment) and at 1 month, 2.8 months, and 5.5 months postbaseline. Eligible participants included patients with newly diagnosed multiple myeloma treated at community oncology practices or academic medical centers in the US. Exposures: GP5 response options were "very much," "quite a bit," "somewhat," "a little bit," and "not at all." Responses at each assessment while undergoing treatment (1 month, 2.8 months, and 5.5 months) were categorized as high adverse event bother (ie, "very much," and "quite a bit") and low adverse event bother (ie, "somewhat," "a little bit," or "not at all"). In addition, change from baseline to each assessment while undergoing treatment was calculated and categorized as worsening by 1 response category and 2 or more response categories. Main Outcome and Measure: ETD due to adverse events (yes vs no) was analyzed using logistic regression adjusting for treatment group, performance status, gender, race, and disease stage. Results: Of the 1087 participants in the original trial, 1058 (mean [SD] age 64 [9] years; 531 receiving VrD [50.2%]; 527 receiving KRd [49.8%]) responded to item GP5 and were included in the secondary analysis. A small proportion (142 patients [13.4%]) discontinued treatment early due to AEs. For those with high adverse-effect bother, GP5 while undergoing treatment was associated with ETD at 1 month (adjusted odds ratio [aOR], 2.20; 95% CI, 1.25-3.89), 2.8 months (aOR, 3.41; 95% CI, 2.01-5.80), and 5.5 months (aOR, 4.66; 95% CI, 1.69-12.83). Worsening by 2 or more response categories on the GP5 was associated with ETD at 2.8 months (aOR, 3.02; 95% CI, 1.64-5.54) and 5.5 months (aOR, 5.49; 95% CI, 1.45-20.76). Conclusions and Relevance: In this survey study of the E1A11 trial, worse GP5 response was associated with ETD. These findings suggest that simple assessment of adverse-effect bother while receiving treatment is an efficient way to indicate treatment tolerability and ETD risk.

Trajectory of health-related quality of life in parents of children treated with epilepsy surgery versus medical therapy.

PURPOSE: Child health-related quality of life (HRQOL) has been shown to improve after epilepsy surgery and is linked to parent HRQOL. We postulated that the HRQOL of parents whose children underwent epilepsy surgery would improve over two years compared to those treated with medical therapy. The aim of the study was to evaluate the trajectory of HRQOL of parents whose children received treatment with epilepsy surgery or medical therapy over two years. METHODS: This multi-center study recruited parents whose children were evaluated for epilepsy surgery. Parents completed measures of care-related QOL (CarerQOL) at the time of their children's surgical evaluation, 6 months, 1 year, and 2 years later. Additional measures included parent anxiety and depression, satisfaction with family relationships, family resources and demands, and child clinical variables. A linear mixed model was used to compare the trajectories of parent HRQOL of surgical and medical patients, adjusting for baseline clinical, parent, and family characteristics. RESULTS: There were 111 children treated with surgery and 154 with medical therapy. The trajectory of parent HRQOL was similar among parents of surgical and medical patients over the two-year follow-up. However, HRQOL of parents of surgical patients was 3.0 points higher (95%CI - 0.1, 6.1) across the follow-up period compared to parents of medical patients. Parents of seizure-free children reported 2.3 points (95%CI 0.2, 4.4) higher HRQOL relative to parents of non-seizure-free children across the two-year follow-up. CONCLUSION: Parent HRQOL did not improve after their children were treated with epilepsy surgery, possibly related to ongoing comorbidities in children.

[Special issue PRO] Considering endpoints for comparative tolerability of cancer treatments using patient report given the estimand framework.

Regulatory agencies are advancing the use of systematic approaches to collect patient experience data, including patient-reported outcomes (PROs), in cancer clinical trials to inform regulatory decision-making. Due in part to clinician under-reporting of symptomatic adverse events, there is a growing recognition that evaluation of cancer treatment tolerability should include the patient experience, both in terms of the overall side effect impact and symptomatic adverse events. Methodologies around implementation, analysis, and interpretation of "patient" reported tolerability are under development, and current approaches are largely descriptive. There is robust guidance for use of PROs as efficacy endpoints to compare cancer treatments, but it is unclear to what extent this can be relied-upon to develop tolerability endpoints. An important consideration when developing endpoints to compare tolerability between treatments is the linkage of trial design, objectives, and statistical analysis. Despite interest in and frequent collection of PRO data in oncology trials, heterogeneity in analyses and unclear PRO objectives mean that design, objectives, and analysis may not be aligned, posing substantial challenges for the interpretation of results. The recent ICH E9 (R1) estimand framework represents an opportunity to help address these challenges. Efforts to apply the estimand framework in the context of PROs have primarily focused on efficacy outcomes. In this paper, we discuss considerations for comparing the patient-reported tolerability of different treatments in an oncology trial context.

Importance of Low- and Moderate-Grade Adverse Events in Patients' Treatment Experience and Treatment Discontinuation: An Analysis of the E1912 Trial.

PURPOSE: Despite defined grades of 1 to 5 for adverse events (AEs) on the basis of Common Terminology Criteria for Adverse Events criteria, mild (G1) and moderate (G2) AEs are often not reported in phase III trials. This under-reporting may inhibit our ability to understand patient toxicity burden. We analyze the relationship between the grades of AEs experienced with patient side-effect bother and treatment discontinuation. METHODS: We analyzed a phase III Eastern Cooperative Oncology Group-American College of Radiology Imaging Network trial with comprehensive AE data. The Likert response Functional Assessment of Cancer Therapy-GP5 item, "I am bothered by side effects of treatment" was used to define side-effect bother. Bayesian mixed models were used to assess the impact of G1 and G2 AE counts on patient side-effect bother and treatment discontinuation. AEs were further analyzed on the basis of symptomatology (symptomatic or asymptomatic). The results are given as odds ratios (ORs) and 95% credible interval (CrI). RESULTS: Each additional G1 and G2 AEs experienced during a treatment cycle increased the odds of increased self-reported patient side-effect bother by 13% (95% CrI, 1.06 to 1.21) and 35% (95% CrI, 1.19 to 1.54), respectively. Furthermore, only AEs defined as symptomatic were associated with increased side-effect bother, with asymptomatic AEs showing no association regardless of grade. Count of G2 AEs increased the odds of treatment discontinuation by 59% (95% CrI, 1.32 to 1.95), with symptomatic G2 AEs showing a stronger association (OR, 1.75; 95% CrI, 1.28 to 2.39) relative to asymptomatic G2 AEs (OR, 1.45; 95% CrI, 1.12 to 1.89). CONCLUSION: Low- and moderate-grade AEs are related to increased odds of increased patient side-effect bother and treatment discontinuation, with symptomatic AEs demonstrating greater magnitude of association than asymptomatic. Our findings suggest that limiting AE capture to grade 3+ misses important contributors to treatment side-effect bother and discontinuation.

Long-term intellectual and developmental outcomes after pediatric epilepsy surgery: A systematic review and meta-analysis.

In addition to the primary aim of seizure freedom, a key secondary aim of pediatric epilepsy surgery is to stabilize and, potentially, optimize cognitive development. Although the efficacy of surgical treatment for seizure control has been established, the long-term intellectual and developmental trajectories are yet to be delineated. We conducted a systematic review and meta-analysis of studies reporting pre- and postsurgical intelligence or developmental quotients (IQ/DQ) of children with focal lesional epilepsy aged ≤18 years at epilepsy surgery and assessed at >2 years after surgery. We determined the IQ/DQ change and conducted a random-effects meta-analysis and meta-regression to assess its determinants. We included 15 studies reporting on 341 patients. The weighted mean age at surgery was 7.1 years (range = .3-13.8). The weighted mean postsurgical follow-up duration was 5.6 years (range = 2.7-12.8). The overall estimate of the mean presurgical IQ/DQ was 60 (95% confidence interval [CI] = 47-73), the postsurgical IQ/DQ was 61 (95% CI = 48-73), and the change was +.94 IQ/DQ (95% CI = -1.70 to 3.58, p = .486). Children with presurgical IQ/DQ ≥ 70 showed a tendency for higher gains than those with presurgical IQ/DQ < 70 (p = .059). Higher gains were determined by cessation of antiseizure medication (ASM; p = .041), not just seizure freedom. Our findings indicate, on average, stabilization of intellectual and developmental functioning at long-term follow-up after epilepsy surgery. Once seizure freedom has been achieved, ASM cessation enables the optimization of intellectual and developmental trajectories in affected children.

Attention and neurodevelopment in young children who are HIV-exposed uninfected.

ABSTRACTChildren HIV-exposed, uninfected (CHEU) are at risk for compromised developmental outcomes. Attention is important for behavioural, cognitive and academic skills, yet has not been thoroughly investigated compared to children HIV-unexposed uninfected (CHUU). Fifty-five CHEU and 51 CHUU children were recruited at 5.5 years of age. Measures of inattention (IA), hyperactivity/impulsivity (HI) and total scores were collected using the parent-reported ADHD-Rating-Scale-IV. Measures of intelligence, visuomotor skills, academics and adaptive functioning were obtained. Analyses of between-group differences were performed as were correlational and multiple regression models, accounting for maternal education, employment and delivery type. Few children met clinical cut-offs for probable ADHD (3.6% CHEU, 2.0% CHUU), and no group differences in measures of IA, HI and combined scores were found. CHEU scored significantly lower than CHUU on intelligence, visuomotor function, academic skills and aspects of adaptive behaviour, though within age expectations. Lower Full-Scale IQ and Processing Speed were associated with higher IA in CHEU and lower adaptive functioning with higher IA in CHUU. Across both groups, children of unemployed mothers had more HI symptoms. CHEU were not at increased risk for attention difficulties at 5.5 years of age. Maternal employment status highlights the contribution of sociodemographic factors in shaping behaviour and neurodevelopment.

Clinical recommendations for conducting pediatric functional language and memory mapping during the phase I epilepsy presurgical workup.

Objective: Pediatric epilepsy surgery effectively controls seizures but may risk cognitive, language, or memory decline. Historically, the intra-carotid anesthetic procedure (IAP or Wada Test) was pivotal for language and memory function. However, advancements in noninvasive mapping, notably functional magnetic resonance imaging (fMRI), have transformed clinical practice, reducing IAP's role in presurgical evaluations. Method: We conducted a critical narrative review on mapping technologies, including factors to consider for discordance. Results: Neuropsychological findings suggest that if pre-surgery function remains intact and the surgery targets the eloquent cortex, there is a high chance for decline. Memory and language decline are particularly pronounced post-left anterior temporal lobe resection (ATL), making presurgical cognitive assessment crucial for predicting postoperative outcomes. However, the risk of functional decline is not always clear - particularly with higher rates of atypical organization in pediatric epilepsy patients and discordant findings from cognitive mapping. We found little research to date on the use of IAP and other newer technologies for lateralization/localization in pediatric epilepsy. Based on this review, we introduce an IAP decision tree to systematically navigate discordance in IAP decisions for epilepsy presurgical workup. Conclusions: Future research should be aimed at pediatric populations to improve the precision of functional mapping, determine which methods predict post-surgical deficits and then create evidence-based practice guidelines to standardize mapping procedures. Explicit directives are needed for resolving conflicts between developing mapping procedures and established clinical measures. The proposed decision tree is the first step to standardize when to consider IAP or invasive mapping, in coordination with the multidisciplinary epilepsy surgical team.

Trajectories of parent well-being in children with drug-resistant epilepsy.

OBJECTIVE: This longitudinal cohort study aimed to identify trajectories of parent well-being over the first 2 years after their child's evaluation for candidacy for epilepsy surgery, and to identify the baseline clinical and demographic characteristics associated with these trajectories. Parent well-being was based on parent depressive and anxiety symptoms and family resources (i.e., family mastery and social support). METHODS: Parents of 259 children with drug-resistant epilepsy (105 of whom eventually had surgery) were recruited from eight epilepsy centers across Canada at the time of their evaluation for epilepsy surgery candidacy. Participants were assessed at baseline and 6-month, 1-year, and 2-year follow-up. The trajectories of parents' depressive symptoms, anxiety symptoms, and family resources were jointly estimated using multigroup latent class growth models. RESULTS: The analyses identified three trajectories: an optimal-stable group with no/minimal depressive or anxiety symptoms, and high family resources that remained stable over time; a mild-decreasing-plateau group with mild depressive and anxiety symptoms that decreased over time then plateaued, and intermediate family resources that remained stable; and a moderate-decreasing group with moderate depressive and anxiety symptoms that decreased slightly, and low family resources that remained stable over time. Parents of children with higher health-related quality of life, fathers, and parents who had higher household income were more likely to have better trajectories of well-being. Treatment type was not associated with the trajectory groups, but parents whose children were seizure-free at the time of the last follow-up were more likely to have better trajectories (optimal-stable or mild-decreasing-plateau trajectories). SIGNIFICANCE: This study documented distinct trajectories of parent well-being, from the time of the child's evaluation for epilepsy surgery. Parents who present with anxiety and depressive symptoms and low family resources do not do well over time. They should be identified and offered supportive services early in their child's epilepsy treatment history.

NCCN Guidelines® Insights: Breast Cancer Screening and Diagnosis, Version 1.2023.

The NCCN Guidelines for Breast Cancer Screening and Diagnosis provide health care providers with a practical, consistent framework for screening and evaluating a spectrum of clinical presentations and breast lesions. The NCCN Breast Cancer Screening and Diagnosis Panel is composed of a multidisciplinary team of experts in the field, including representation from medical oncology, gynecologic oncology, surgical oncology, internal medicine, family practice, preventive medicine, pathology, diagnostic and interventional radiology, as well as patient advocacy. The NCCN Breast Cancer Screening and Diagnosis Panel meets at least annually to review emerging data and comments from reviewers within their institutions to guide updates to existing recommendations. These NCCN Guidelines Insights summarize the panel's decision-making and discussion surrounding the most recent updates to the guideline's screening recommendations.

Pre-Operative Predictors of Health-Related Quality of Life Two Years After Pediatric Epilepsy Surgery: A Prospective Cohort Study.

PURPOSE: Seizure freedom is an important predictor of health-related quality of life (HRQOL) after pediatric epilepsy surgery. This study aimed to identify the pre-operative predictors of HRQOL 2 years after epilepsy surgery in children with drug-resistant epilepsy. METHODS: This multicenter prospective cohort study assessed pre-operative predictors including child (demographics and clinical variables), caregiver (including caregiver depressive and anxiety symptoms) and family characteristics. HRQOL was assessed using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE)-55 pre-operatively and 2-years after surgery. Univariable linear regression analyses were done to identify significant preoperative predictors of HRQOL 2-years after surgery, followed by multivariable regression. RESULTS: Ninety-five children underwent surgery, mean age was 11.4 (SD=4.2) years, and 59 (62%) were male. Mean QOLCE scores were 57.4 (95%CI: 53.8, 61.0) pre-operatively and 65.6 (95%CI: 62.0, 69.1) after surgery. Univariable regression showed fewer anti-seizure medications (ß=-6.1 [95%CI: -11.2, -1.0], p = 0.019), older age at seizure onset (ß=1.6 [95%CI: 0.8, 2.4], p<0.001), higher pre-operative HRQOL (ß=0.7 [95%CI: 0.5, 0.8], p<0.001), higher family resources (ß=0.6 [95%CI: 0.3, 0.9], p<0.001), better family relationships (ß=1.7 [95%CI: 0.3, 3.1], p = 0.017) and lower family demands (ß=-0.9 [95%CI: -1.5, -0.4], p<0.001) were associated with higher HRQOL after surgery. Caregiver characteristics did not predict HRQOL after surgery (p>0.05). Multivariable regression showed older age at seizure onset (ß=4.6 [95%CI: 1.6, 7.6], p = 0.003) and higher pre-operative HRQOL (ß=10.2 [95%CI: 6.8, 13.6], p<0.001) were associated with higher HRQOL after surgery. CONCLUSION: This study underscores the importance of optimizing pre-operative HRQOL to maximize HRQOL outcome after pediatric epilepsy surgery.

Standardized Definitions for Efficacy End Points in Neoadjuvant Breast Cancer Clinical Trials: NeoSTEEP.

PURPOSE: The Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007 and updated in 2021 (STEEP 2.0), provide standardized definitions of adjuvant breast cancer (BC) end points. STEEP 2.0 identified a need to separately address end points for neoadjuvant clinical trials. The multidisciplinary NeoSTEEP working group of experts was convened to critically evaluate and align neoadjuvant BC trial end points. METHODS: The NeoSTEEP working group concentrated on neoadjuvant systemic therapy end points in clinical trials with efficacy outcomes-both pathologic and time-to-event survival end points-particularly for registrational intent. Special considerations for subtypes and therapeutic approaches, imaging, nodal staging at surgery, bilateral and multifocal diseases, correlative tissue collection, and US Food and Drug Administration regulatory considerations were contemplated. RESULTS: The working group recommends a preferred definition of pathologic complete response (pCR) as the absence of residual invasive cancer in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0 per AJCC staging). Residual cancer burden should be a secondary end point to facilitate future assessment of its utility. Alternative end points are needed for hormone receptor-positive disease. Time-to-event survival end point definitions should pay particular attention to the measurement starting point. Trials should include end points originating at random assignment (event-free survival and overall survival) to capture presurgery progression and deaths as events. Secondary end points adapted from STEEP 2.0, which are defined from starting at curative-intent surgery, may also be appropriate. Specification and standardization of biopsy protocols, imaging, and pathologic nodal evaluation are also crucial. CONCLUSION: End points in addition to pCR should be selected on the basis of clinical and biologic aspects of the tumor and the therapeutic agent investigated. Consistent prespecified definitions and interventions are paramount for clinically meaningful trial results and cross-trial comparison.

NCCN Guidelines® Insights: Breast Cancer, Version 4.2023.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer address all aspects of management for breast cancer. The treatment landscape of metastatic breast cancer is evolving constantly. The therapeutic strategy takes into consideration tumor biology, biomarkers, and other clinical factors. Due to the growing number of treatment options, if one option fails, there is usually another line of therapy available, providing meaningful improvements in survival. This NCCN Guidelines Insights report focuses on recent updates specific to systemic therapy recommendations for patients with stage IV (M1) disease.

A longitudinal cohort study of mediators of health-related quality of life after pediatric epilepsy surgery or medical treatment.

OBJECTIVES: The purpose of this longitudinal cohort study was to examine the variables that influence health-related quality of life (HRQOL) after epilepsy surgery in children. We examined whether treatment type (surgical vs medical therapy) and seizure control are related to other variables that have been shown to influence HRQOL, namely depressive symptoms in children with epilepsy or their parents, and the availability of family resources. METHODS: In total, 265 children with drug-resistant epilepsy were recruited from eight epilepsy centers across Canada at the time of their evaluation for candidacy for epilepsy surgery and were assessed at baseline, 6-month, 1-year, and 2-year follow-up. Parents completed the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) and measures of family resources and depression; children completed depression inventories. Causal mediation analyses using natural effect models were used to evaluate the extent to which the relationship between treatment and HRQOL was explained by seizure control, child and parent depressive symptoms, and family resources. RESULTS: Overall, 111 children underwent surgery and 154 were treated with medical therapy only. The HRQOL scores of surgical patients were 3.4 points higher (95% confidence interval [CI]: -0.2, 7.0) relative to medical patients at the 2-year follow-up after adjusting for baseline covariates, with 66% of the effect of surgery attributed to seizure control. Child or parent depressive symptoms and family resources had negligible mediation effects between treatment and HRQOL. The effect of seizure control on HRQOL was not mediated by child or parent depressive symptoms, or by family resources. SIGNIFICANCE: The findings demonstrate that seizure control is on the causal pathway between epilepsy surgery and improved HRQOL in children with drug-resistant epilepsy. However, child and parent depressive symptoms and family resources were not significant mediators. The results highlight the importance of achieving seizure control to improve HRQOL.

Trajectory of Health-Related Quality of Life After Pediatric Epilepsy Surgery.

Importance: Health-related quality of life (HRQOL) is regarded as a key outcome for evaluating treatment efficacy. However, it is uncertain how HRQOL evolves after epilepsy surgery compared with medical therapy, such as whether it continues to improve over time, improves and then remains stable, or deteriorates after a period of time. Objective: To assess trajectory of HRQOL over 2 years in children with drug-resistant epilepsy (DRE) treated with surgery compared with medical therapy. Design, Setting, and Participants: Prospective cohort study assessing HRQOL longitudinally over 2 years. Participants were children recruited from 8 epilepsy centers in Canada from 2014 to 2019 with suspected DRE aged 4 to 18 years who were evaluated for surgery. Data were analyzed from May 2014 to December 2021. Exposures: Epilepsy surgery or medical therapy. Main Outcomes and Measures: HRQOL was measured using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE)-55. HRQOL and seizure frequency were assessed at baseline, 6-month, 1-year, and 2-year follow-ups. Clinical, parent, and family characteristics were assessed at baseline. A linear mixed model was used to evaluate HRQOL over time, adjusting for baseline clinical, parent, and family characteristics. Results: There were 111 surgical and 154 medical patients (mean [SD] age at baseline was 11.0 [4.1] years; 118 [45%] were female). At baseline, HRQOL was similar among surgical and medical patients. HRQOL of surgical patients was 3.0 (95% CI, -0.7 to 6.8) points higher at 6-month, 4.9 (95% CI, 0.7 to 9.1) points higher at 1-year, and 5.1 (95% CI, 0.7 to 9.5) points higher at 2-year follow-ups compared with medical patients. Surgical patients experienced greater improvements in social functioning relative to medical patients, but not for cognitive, emotional, and physical functioning. At 2-year follow-up, 72% of surgical patients were seizure-free, compared with 33% of medical patients. Seizure-free patients reported higher HRQOL than those who were not. Conclusions and Relevance: This study provided evidence on the association between epilepsy surgery and children's HRQOL, with improvement in HRQOL occurring within the first year and remaining stable 2 years after surgery. By demonstrating that surgery improved seizure freedom and HRQOL, which has downstream effects such as better educational attainment, reduced health care resource utilization, and health care cost, these findings suggest that the high costs of surgery are justified, and that improved access to epilepsy surgery is necessary.

Oncologist-Reported Barriers and Facilitators to Enrolling Patients in Optimization Trials That Test Less Intense Cancer Treatment.

PURPOSE: As outcomes improve in early-stage breast cancer, clinical trials are undergoing a paradigm shift from intensification trials (more therapy) to improve survival to optimization trials, which assess the potential for using less toxic therapy while preserving survival outcomes. However, little is known about physician perspectives in community and academic settings about possible barriers and facilitators that could affect accrual to optimization clinical trials and the generalizability of future findings. METHODS: We conducted a qualitative study with semistructured interviews of medical oncologists from different academic and community practices to assess their perspectives on optimization trials. Interviews were audio-recorded and transcribed. Three independent coders used a content analysis approach to analyze transcripts using NVivo. Major themes and exemplary quotes were extracted. RESULTS: All 39 physicians reported that they would enroll patients in optimization clinical trials. Oncologists highlighted specific reasons to consider optimization trials. These included quality-of-life improvement by reducing toxicity, reduction in financial toxicity, fertility preservation, ability to avoid chemotherapy, minimization of overtreatment in patients with comorbid conditions, personalized treatment, opportunities to test novel therapies, and leveraging the availability of targeted therapies. Oncologists also identified accrual barriers, such as tumor-specific biology, individual (host) factors, prognostic markers of risk, access to therapies, provider experience, and system constraints. They voiced recommendations regarding preliminary data, trial design, and tools to support enrollment in optimization trials. CONCLUSION: Although oncologists are generally willing to enroll patients on optimization clinical trials, barriers affect their acceptance. A scientific focus on overcoming these barriers is needed to support future enrollment on trials tailoring therapy on the basis of risk and potential benefit to allow true personalization of treatment.

Infrastructure to Support Accrual of Older Adults to National Cancer Institute Clinical Trials.

As part of ongoing efforts to meaningfully improve recruitment, enrollment, and accrual of older adults into cancer clinical trials, the National Cancer Institute (NCI) sponsored a workshop with experts across the country entitled Engaging Older Adults in the NCI Clinical Trials Network: Challenges and Opportunities. Three working groups, including Study Design, Infrastructure, and Stakeholders, were formed, who worked together to offer synergistic improvements in the system. Here, we summarize the workshop discussions of the Infrastructure Working Group, whose goal was to address infrastructural challenges, identify underlying resources, and offer solutions to facilitate accrual of older adults into cancer clinical trials. Based on preconference work and workshop discussions, four key recommendations to strengthen NCI infrastructure were proposed: 1) further centralize resources and expertise; 2) provide training for clinical research staff; (3) develop common data elements; and 4) evaluate what works and does not work. These recommendations provide a strategy to improve the infrastructure to enroll more older adults in cancer clinical trials.