Pre-operative predictors of post-operative seizure control in low-grade glioma: a systematic review and meta-analysis.

As many as 80% of low-grade gliomas (LGGs) present with seizures, negatively impacting quality of life. While seizures are associated with gliomas regardless of grade, the importance of minimizing impact of seizures for patients with low grade tumors cannot be understated given the prolonged survival period in this population. The objective of this systematic review and meta-analysis was to summarize existing literature and identify factors associated with post-operative seizure control (defined as Engel I classification) in patients with LGGs, with a focus on pre-operative factors. Patient data extracted include tumor location and histology, pre-operative anti-seizure medication use, extent of resection (EOR), adjuvant treatment, pre-operative seizure type, duration, and frequency, and post-operative Engel classification. A random-effects model was used to calculate the effects of EOR, pre-operative seizure duration, adjuvant radiation, and adjuvant chemotherapy on post-operative seizure control. The effect of tumor location and histology on post-operative Engel I classification was determined using contingency analyses. Thirteen studies including 1628 patients with seizures were included in the systematic review. On meta-analyses, Engel I classification was associated with pre-operative seizure type (OR = 0.79 (0.63-0.99), p = 0.0385, focal versus generalized), frontal lobe LGGs (OR = 1.5 (1.1-2.0), p = 0.0195), and EOR (OR (95% CI) = 4.5 (2.3-6.7), p < 0.0001 gross-total versus subtotal). Pre-operative seizure duration less than one year, adjuvant radiation, adjuvant chemotherapy, and tumor histology were not associated with achieving Engel I classification. In addition to the known effects of EOR, Engel I classification is less likely to be achieved in patients with focal pre-operative seizures and more likely to be achieved in patients with frontal lobe LGGs.

Long-term antiseizure medication use in patients after meningioma resection: identifying predictors for successful weaning and failures.

OBJECTIVE: To define risk factors for meningioma-related seizures and predictors of successful weaning of antiseizure medications following meningioma resection. METHODS: This is a retrospective study of 95 patients who underwent meningioma resection at a single institution. Primary outcome analyzed was ability to achieve seizure freedom without the use of anti-seizure medication at 6-months, 1-year, and last known follow up. Secondary outcome was postoperative seizure freedom. RESULTS: Preoperative seizures (OR: 11.63, 95% CI [3.64, 37.17], p < 0.0001), non-skull base tumor location (OR: 3.01, 95% CI [1.29, 7.02], p = 0.0128), and modified STAMPE score of 3-5 (OR: 5.42, 95% CI [2.18, 13.52], p = 0.0003) were associated with greater likelihood of remaining on antiseizure medication at 6-month follow up. Preoperative seizures (OR: 4.93, 95% CI: [2.00, 12.16 ], p = 0.0008), intratumoral calcifications (OR: 4.19, 95% CI: [1.61, 14.46], p = 0.0055), modified STAMPE score of 3-5 (OR: 5.42, CI [2.18, 13.52], p = 0.0003), and Ki67 greater than 7% (OR: 5.68, CI [1.61, 20.10], p = 0.0060) were significant risk factors for inability to discontinue ASMs by last follow up. Preoperative seizures (OR: 4.33, 95% CI [1.59, 11.85], p = 0.0050) and modified STAMPE score of 3-5 (OR: 6.09, 95% CI [2.16, 17.20], p = 0.0007) were significant risk factors for postoperative seizures. CONCLUSIONS: Preoperative seizures, modified STAMPE2 score of 3-5, non-skull base tumor location, intratumoral calcifications, and Ki67 > 7% were significant risk factors for inability to achieve seizure freedom without ASMs. In addition, the modified STAMPE2 score successfully predicted increased seizure risk following meningioma resection for patients with a score of 3 or higher.

Trajectories of Current and Predicted Satisfaction With One's Life Following a Cancer Diagnosis.

Background: Poor physical and mental health is common among cancer survivors, but little is known about how cancer influences life satisfaction and expectations about one's future, both of which may subsequently influence health decisions and outcomes. Purpose: The current study examined how a cancer diagnosis influences current and predicted future life satisfaction in seven domains, including family, finances, work, and health. Methods: We leveraged data from three waves of the Midlife in the United States study (N = 6,389) and examined the relation between new and past cancer diagnoses on satisfaction using generalized estimating equations. We also compared participants' predicted satisfaction to the actual satisfaction they reported at later waves of data collection, and examined whether concordance between the two differed by cancer history. Results: A cancer diagnosis was associated with a decline in satisfaction about one's present health and sex life, ps < .05, but satisfaction with all other domains remained steady or improved. In contrast, predictions about the future became and remained less optimistic than the predictions of those without cancer across all life domains except relationships with children, ps < .05. Within-subjects comparisons of predicted and actual satisfaction suggest those without a cancer history were optimistic in their predictions across all life domains except health whereas survivors were more accurate in their predictions. Conclusions: Given the many ways in which expectations about the future can influence decision making, behavior, and health, survivors' attenuated optimistic outlooks may influence their health and well-being.

Phase Ib with expansion study of olaparib plus weekly (Metronomic) carboplatin and paclitaxel in relapsed ovarian cancer patients.

OBJECTIVE: Our goals were to: establish the maximum-tolerated dose of olaparib tablets combined with metronomic carboplatin and paclitaxel in patients with relapsed high-grade serous ovarian cancer; evaluate dose-limiting toxicities; and evaluate efficacy at the maximum tolerated dose. METHODS: In this open-label, single-arm, investigator-initiated trial (ClinicalTrials.gov NCT01650376), patients with high-grade serous ovarian cancer who failed primary platinum and taxane therapy received oral olaparib tablets twice daily days 1-3 each week combined with fixed-dose metronomic carboplatin AUC2 and paclitaxel 60 mg/m2 weekly for 3 out of 4 weeks. A 3 × 3 design was used to determine the olaparib maximum tolerated dose. Combination therapy continued until disease progression, but patients with partial or complete response were transitioned to olaparib maintenance therapy. All patients were included in the analysis. RESULTS: The maximum tolerated dose of olaparib tablets was 150 mg twice daily with metronomic carboplatin and paclitaxel. 54 women were enrolled, 14 in phase Ib and 40 in the expansion phase. The median number of prior therapeutic regimens was 3. Response included 13 complete remission (24%) and 16 partial remission (30%) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) for an overall response rate of 54% (95% CI 40% to 67%). Of 47 patients who underwent BRCA testing, 23 were BRCA mutation (BRCAm) and 24 B RCA wild type (BRCAwt). Progression-free survival for BRCAm was 12.1 months versus 4.8 for BRCAwt (p=0.0001). Median overall survival for BRCAm was 24.1 months versus 10.4 months for BRCAwt (p=0.02). 42 patients (78%) experienced grade 3-4 toxicities with combination therapy; the most common were hematologic. There were no treatment related deaths. Among 14 patients who received maintenance therapy, 7 experienced grade 1-2 non-hematologic toxicities. CONCLUSIONS: Olaparib 150 mg tablet twice daily can be safely administered in combination with metronomic carboplatin and paclitaxel in pre-treated relapsed ovarian cancer with 24% complete remission. BRCAm patients had statistically significant longer progression-free survival and overall survival than BRCAwt. TRIAL REGISTRATION NUMBER: NCT01650376.

Social support, loneliness, eating, and activity among parent-adolescent dyads.

We examined associations of social support and loneliness with eating and activity among parent-adolescent dyads (N = 2968) using actor-partner interdependence modeling. Loneliness had several actor associations with health behaviors (adolescents: less physical activity [PA], p < .001, more sedentariness, p < .001; parents: less fruit/vegetable consumption [FVC], p = .029, more hedonic food consumption [HFC], p = .002, and sedentariness, p < .001), but only one dyadic association (adolescent loneliness with less parent FVC, p = .039). Visible support was associated with less HFC, p < .001, and sedentariness, p < .001, but less FVC, p = .008, among adolescents. Invisible support was associated with less HFC, p = .003, but also less PA, p = .028, among adolescents. Both support types were associated with less HFC among parents, p < .001, but invisible support was also associated with less FVC, p = .029, and PA, p = .012, and more sedentariness, p = .013, among parents. When examining health behavior among parents and adolescents, it may be important to consider social support (but perhaps not loneliness) at a dyadic level.

Interventions to Engage Affective Forecasting in Health-Related Decision Making: A Meta-Analysis.

Background: People often use affective forecasts, or predictions about how a decision will make them feel, to guide medical and health decision making. However, these forecasts are susceptible to biases and inaccuracies that can have consequential effects on decision making and health. Purpose: A meta-analysis was performed to determine the effectiveness of intervening to address affective forecasting as a means of helping patients make better health-related choices. Methods: We included between-subjects experimental and intervention studies that targeted variables related to affective forecasting (e.g., anticipated regret, anticipated affect) as a means of changing health behaviors or decisions. We determined the overall effect of these interventions on targeted affective constructs and behavioral outcomes, and whether conceptual and methodological factors moderated these effects. Results: A total of 133 independent effect sizes were identified from 37 publications (N = 72,020). Overall, affective forecasting interventions changed anticipated regret, d = 0.24, 95% confidence interval (CI) (0.15, 0.32), p < .001, behavior, d = 0.29, 95% CI (0.13, 0.45), p < .001, and behavioral intentions, d = 0.19, 95% CI (0.11, 0.28), p < .001, all measured immediately postintervention. Interventions did not change anticipated positive and negative affect, and effects on intentions and regret did not extend to follow-up time points, ps > .05. Generally, effects were not moderated by conceptual model, intervention intensity, or behavioral context. Conclusions: Affective forecasting interventions had a small consistent effect on behavioral outcomes regardless of intervention intensity and conceptual framework, suggesting such constructs are promising intervention targets across several health domains.

Sex Differences in the Association of Perceived Ambiguity, Cancer Fatalism, and Health-Related Self-Efficacy with Fruit and Vegetable Consumption.

Adequate fruit and vegetable (FV) consumption is promoted as a means of preventing chronic health conditions, such as cardiovascular disease and cancer. This study investigated whether perceived ambiguity about cancer prevention recommendations, fatalistic beliefs about cancer, and health-related self-efficacy were associated with FV consumption and whether sex moderated these associations. Data from the five most recent waves (spanning 2011 to 2017) of the nationally representative Health Information National Trends Survey (N = 16,965) were used. Participants reported levels of perceived ambiguity, cancer fatalism, health-related self-efficacy, and daily FV consumption. Perceived ambiguity and cancer fatalism were negatively associated with FV consumption, ps <.001, whereas health-related self-efficacy was positively associated with FV consumption, b = 0.34, p < .001. Sex moderated these associations, ps <.05. Perceived ambiguity and cancer fatalism were more strongly associated with less FV consumption for men, bs < -0.31, ps <.001, than women, bs < -0.14, ps <.01. In contrast, health-related self-efficacy was more strongly associated with more FV consumption for women, b = 0.43, p < .001, than men, b = 0.26, p < .001. These results suggest that tailoring health messaging to target sex-specific barriers may improve their effectiveness.

Factors beyond Lack of Knowledge That Predict "I Don't Know" Responses to Surveys That Assess HPV Knowledge.

Accurately assessing the public's knowledge about the human papilloma virus (HPV) and the HPV vaccine remains critical for informing health education interventions aimed at increasing vaccine uptake. Responding "don't know" (DK) to survey questions that assess knowledge is common and DK responders are often systematically different from other responders, resulting in potential for bias. This study aimed to advance our understanding of DK responding to HPV knowledge items. Data from the nationally representative Health Information National Trends Survey Wave 5 Cycle 1 (N = 2,034) were used. Information seeking about cancer, information avoidance, health-related self-efficacy, and several cancer beliefs were examined as predictors of DK responding to six items that assessed HPV knowledge. DKs represented nearly half of responses. Adjusting for demographic factors, lower health-related self-efficacy, and greater information avoidance, cancer-mortality salience, and perceived ambiguity were associated with more DK responding, ps < .05. Even participants with incorrect responses had greater health-related self-efficacy, and less information avoidance, perceived ambiguity, and cancer-mortality salience than those who responded with DK. DK responding to HPV knowledge items is common and reflects factors beyond insufficient knowledge or motivation. Addressing causes of DK responding may reduce bias and improve interventions informed by surveys.

Unpacking cancer patients' preferences for information about their care.

OBJECTIVE: Patient-centered decision making requires cancer patients be actively involved and feel sufficiently informed about their care, but patients' preferences for information are often unrecognized or unmet by their oncologist, particularly for more distressing topics. This study examined cancer patients' preferences for information about three care-related topics: (1) diagnostic information, (2) treatment costs, and (3) prognosis. We tested whether factors known to influence information preferences (psychological distress, control preferences, and financial distress) were differently associated with information preferences for each topic. METHODS: Cancer patients (N = 176) receiving ongoing treatment completed a questionnaire that assessed their out-of-pocket treatment costs, psychological distress, preferences for control over their medical decisions, and the amount of information they desired and received from their oncologists about the three topics. RESULTS: Patients' preferences were less often met for treatment cost information than for the other topics, p < 0.001, with half wanting more cost information than they received. One-third of patients also wanted more prognostic information than they received. Patients' preferences for diagnostic information did not differ as a function of financial burden, distress, or control preferences, ps > 0.05. Preferences for cost information were greater among patients who preferred more control over their medical decisions, p = 0.016. Patients' preferences for prognostic information were greater among those desiring more control and with lower distress, ps < 0.05. Financial burden was not associated with information preferences. CONCLUSION: Appreciating the variability in information preferences across topics and patients may aid efforts to meet patients' information needs and improve outcomes.

Patient Attitudes Regarding the Cost of Illness in Cancer Care.

BACKGROUND AND PURPOSE: The cost of illness in cancer care and the subsequent distress has attracted scrutiny. Guidelines recommend enhanced discussion of costs, assuming this will reduce both stress and costs. Little is known about patient attitudes about cost considerations influencing treatment decisions. METHODS: A convenience-sample survey of patients currently receiving radiation and/or intravenous chemotherapy at an outpatient cancer center was performed. Assessments included prevalence and extent of financial burden, level of financial distress, attitudes about using costs to influence treatment decisions, and frequency or desirability of cost discussions with oncologists. RESULTS: A total of 132 participants (94%) responded. Overall, 47% reported high financial stress, 30.8% felt well informed about costs prior to treatment, and 71% rarely spoke to their oncologists about cost. More than 71% of patients did not want either society's or personal costs to influence treatment, and this result did not change based on degree of financial stress. Even when asked to assume that lower cost regimens were equally effective, only 28% would definitely want the lower cost regimen. Patients did not believe it was the oncologist's duty to perform cost discussions. CONCLUSION: Even insured patients have a high degree of financial distress. Most, including those with the highest levels of distress, did not speak often with oncologists about costs and were strongly adverse to having cost considerations influence choice of regimen. The findings suggest that patients are not cost sensitive with regard to treatment decisions. Oncologists will require improved tools to have meaningful cost discussion, as recommended by the American Society of Clinical Oncology.

Worry about skin cancer mediates the relation of perceived cancer risk and sunscreen use.

Preventive health behaviors are believed to be motivated in part by a person's perception of risk for a particular health problem. Risk contains a cognitive component, beliefs about the chances of a health problem occurring, and an affective component, fear or worry about the health problem. Although both have been shown to influence behavior, the nature of their interrelation as an influence on behavior has not been examined. Data from the 2005 Health Information National Trends Survey, a US nationally-representative telephone survey was analyzed. Participants reported perceived absolute and comparative risk for skin cancer, feelings of worry about skin cancer, and sunscreen use behavior. Analyses examined main effects models for the relation between perceived risk, worry, and sunscreen use, as well as both moderated and mediated models. For both absolute and comparative risk, the relation between cognitively-based perceived risk for skin cancer and sunscreen use was fully mediated by feelings of worry, as evidenced by significant direct effects of worry (bs > 0.046, ps < 0.01) and indirect effects of risk through worry (bs > 0.19, ps < 0.01). When worry was included in the models, direct effects of risk perceptions were non-significant (bs < 0.11, ps < 0.10). No evidence was found for moderated effects of worry on the relation between risk and behavior. While cognitive risk appraisals do influence decision making and may be addressed by interventions, these findings demonstrate that affectively-based risk components play a key role in behavior regulation. Affectively-based risk might be an effective target for interventions and should be incorporated more fully in decision-making models.

Implicit affective associations predict snack choice for those with low, but not high levels of eating disorder symptomatology.

The central purpose of the current study was to examine whether eating disorder symptomatology moderates the extent to which implicitly and explicitly measured affective associations with fruits, or the feelings individuals associate with them, predict food choice. Participants (N = 107) completed both implicit and explicit measures of affective associations with fruits, a self-report of eating disorder symptomatology. In a subsequent snack selection task, they selected either a granola bar or fruit as a measure of their food choice behavior. Logistic regression analyses revealed that eating disorder symptomatology moderated the relation of implicit affective associations on behavior, OR = 0.27, p = .024, 95% CI (0.085, 0.84). A test of the simple effects indicated that implicit affective associations predicted snack choice at or below mean symptomatology levels [OR = 2.073, p = .02, 95% CI (1.12, 3.84)], but not at high levels [OR = 0.56, p = .28, 95% CI (0.18, 1.74)]. The effects of explicit measures on eating behavior were not moderated by eating disorder symptomatology (ps > .05). These findings advance our understanding of both the relation of implicit affective associations on behavior, as well as the ways in which eating disorder symptomatology may impact the decision-making process, thereby perpetuating disorder-related eating behavior. As such, they have implications for both health decision-making theory, as well as for the study and treatment of eating disorders.

Patterns of Antiseizure Medication Use Following Meningioma Resection: A Single-Institution Experience.

OBJECTIVE: To investigate antiseizure medication (ASM) practice behavior for patients who present with seizures before meningioma resection and to review postoperative ASM management. METHODS: A retrospective study was performed of 112 consecutive patients with meningiomas who underwent resection at a single institution between October 2016 and January 2020. Data were collected through detailed chart review. RESULTS: Of 112 patients, 35 (31%) had a preoperative seizure, and 43 (38%) were prescribed a preoperative ASM. At discharge, 96 patients (86%) were prescribed an ASM, most often 1000 mg daily of levetiracetam (64%, 61/96) and less often higher doses of levetiracetam or other ASMs. By the 6-month postoperative visit, 55 patients (49%) were taking at least 1 ASM, most commonly levetiracetam monotherapy (65%) at 500 mg twice daily (47%). This number further decreased to 45 (40%) patients by 1-year follow-up and 36 (32%) patients by last-known follow-up. By last follow-up (median 27.3 months; range 5.4-57.4 months), 24 patients (21%) had experienced a postoperative seizure, and 36 patients (32%) were never able to discontinue ASMs. Of patients remaining on levetiracetam monotherapy, only 36% remained on levetiracetam 500 mg twice daily. CONCLUSIONS: Approximately two thirds (68%) of patients who underwent surgical resection of meningioma were eventually able to completely discontinue their postoperative ASM regimen. However, nearly one third (32%) of patients required long-term ASM management. Levetiracetam monotherapy was the most common ASM prescribed during the postoperative period, and the proportion of patients requiring either higher doses of levetiracetam or alternative ASMs increased over time.

Impact of Postoperative Stereotactic Body Radiation Therapy on Survival of Patients with Spinal Metastases in the Context of Additional Systemic Adjuvant Therapy.

BACKGROUND: Stereotactic body radiotherapy (SBRT) has been established as a safe and effective treatment modality for control of long-term pain and tumor growth. However, few studies have investigated the efficacy of postoperative SBRT versus conventional external beam radiation therapy (EBRT) in extending survival within the context of systemic therapy. METHODS: A retrospective chart review of patients who underwent surgery for spinal metastasis at our institution was conducted. Demographic, treatment, and outcome data were collected. SBRT was compared with EBRT and non-SBRT, and analyses were stratified by whether patients received systemic therapy. Survival analysis was conducted using propensity score matching. RESULTS: Bivariate analysis in the nonsystemic therapy group revealed longer survival with SBRT compared with EBRT and non-SBRT. Further analysis also showed that primary cancer type and preoperative mRS significantly affected survival. Within patients who received systemic therapy, overall median survival for patients receiving SBRT was 22.7 months (95% confidence interval [CI] 12.1-52.3) versus 16.1 months (95% CI 12.7-44.0; P = 0.28) for patients who received EBRT and 16.1 months (95% CI: 12.2-21.9; P = 0.07) for patients without SBRT. Within patients who did not receive systemic therapy, overall median survival for patients with SBRT was 62.1 months (95% CI 18.1-unknown) versus 5.3 months (95% CI 2.8-unknown; P = 0.08) for patients with EBRT and 6.9 months (95% CI 5.0-45.6; P = 0.02) for patients without SBRT. CONCLUSIONS: In patients who do not receive systemic therapy, treatment with postoperative SBRT may increase survival time compared with patients not receiving SBRT.

Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer.

Importance: There has been little consideration of genomic risk of recurrence by breast cancer subtype despite evidence of racial disparities in breast cancer outcomes. Objective: To evaluate associations between clinical trial end points, namely pathologic complete response (pCR) and distant recurrence-free survival (DRFS), and race and examine whether gene expression signatures are associated with outcomes by race. Design, Setting, and Participants: This retrospective cohort study used data from the Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2 (I-SPY 2) multicenter clinical trial of neoadjuvant chemotherapy with novel agents and combinations for patients with previously untreated stage II/III breast cancer. Analyses were conducted of associations between race and short- and long-term outcomes, overall and by receptor subtypes, and their association with 28 expression biomarkers. The trial enrolled 990 female patients between March 30, 2010, and November 5, 2016, with a primary tumor size of 2.5 cm or greater and clinical or molecular high risk based on MammaPrint or hormone receptor (HR)-negative/ERBB2 (formerly HER2 or HER2/neu)-positive subtyping across 9 arms. This data analysis was performed between June 10, 2021, and October 20, 2022. Exposure: Race, tumor receptor subtypes, and genomic biomarker expression of early breast cancer. Main Outcomes and Measures: The primary outcomes were pCR and DRFS assessed by race, overall, and by tumor subtype using logistic regression and Cox proportional hazards regression models. The interaction between 28 expression biomarkers and race, considering pCR and DRFS overall and within subtypes, was also evaluated. Results: The analytic sample included 974 participants (excluding 16 self-reporting as American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, or multiple races due to small sample sizes), including 68 Asian (7%), 120 Black (12%), and 786 White (81%) patients. Median (range) age at diagnosis was 47 (25-71) years for Asian, 49 (25-77) for Black, and 49 (23-73) years for White patients. The pCR rates were 32% (n = 22) for Asian, 30% for Black (n = 36), and 32% for White (n = 255) patients (P = .87). Black patients with HR-positive/ERBB2-negative tumors not achieving pCR had significantly worse DRFS than their White counterparts (hazard ratio, 2.28; 95% CI, 1.24-4.21; P = .01), with 5-year DRFS rates of 55% (n = 32) and 77% (n = 247), respectively. Black patients with HR-positive/ERBB2-negative tumors, compared with White patients, had higher expression of an interferon signature (mean [SD], 0.39 [0.87] and -0.10 [0.99]; P = .007) and, compared with Asian patients, had a higher mitotic score (mean [SD], 0.07 [1.08] and -0.69 [1.06]; P = .01) and lower estrogen receptor/progesterone receptor signature (mean [SD], 0.31 [0.90] and 1.08 [0.95]; P = .008). A transforming growth factor ß signature had a significant association with race relative to pCR and DRFS, with a higher signature associated with lower pCR and worse DRFS outcomes among Black patients only. Conclusions and Relevance: The findings show that women with early high-risk breast cancer who achieve pCR have similarly good outcomes regardless of race, but Black women with HR-positive/ERBB2-negative tumors without pCR may have worse DRFS than White women, highlighting the need to develop and test novel biomarker-informed therapies in diverse populations.

Meningeal defects and focal cortical dysplasia: an unrecognized relationship? Illustrative case.

BACKGROUND: Focal cortical dysplasias (FCDs) are a heterogenous cluster of histopathologic entities classically associated with medically refractory epilepsy. Because there is substantial histopathologic variation among different types of FCD, there are likely multiple pathogenic mechanisms leading to these disorders. The meninges are known to play a role in cortical development, and disruption of meningeal-derived signaling pathways has been shown to impact neurodevelopment. To our knowledge, there has not yet been an investigation into whether genetic pathways regulating meningeal development may be involved in the development of FCD. OBSERVATIONS: The authors reported a patient with refractory epilepsy and evidence of FCD on imaging who received surgical intervention and was found to have an unusual dural anomaly overlying a region of type Ic FCD. To the authors' knowledge, this was the first report describing a lesion of this nature in the context of FCD. LESSONS: The dural anomaly exhibited by the patient presented what could be a potentially novel pathogenic mechanism of FCD. Resection of the cortical tissue underlying the dural anomaly resulted in improvement in seizure control. Although the pathogenesis is unclear, this case highlighted the importance of further investigation into the developmental origins of FCD, which may help elucidate whether a connection between meningeal development and FCD exists.

Characteristics of Scientific Evidence Informing Changed U.S. Preventive Services Task Force Insufficient Evidence Statements.

INTRODUCTION: The U.S. Preventive Services Task Force (USPSTF) issues "Insufficient Evidence" (I) statements when scientific evidence is inadequate for making recommendations about clinical preventive services. Insufficient Evidence statements may be changed to definitive recommendations if new research closes evidence gaps. This study examines the characteristics of evidence that informed changes from I statements to definitive recommendations, including NIH's role as a funder. METHODS: A total of 11 USPSTF Insufficient Evidence statements that were changed between 2010 and 2019 were assessed. Study designs, bibliometric influence, and funding sources for scientific articles cited in USPSTF evidence reviews were characterized for each I statement. Data were analyzed in 2019-2020. RESULTS: Most I statements (82%) changed to a B grade; an average of 8.4 years elapsed between issuing the I statement and releasing the definitive recommendation. An average of 63 (range=19-253) articles were included in each USPSTF evidence review. NIH support was cited in 28.8% of articles, on average. The proportion of NIH-funded articles reporting RCT designs was similar to that of non-NIH-funded articles (64.5% vs 59.5%). A higher proportion of NIH-funded articles were rated good quality for study design (39.0%) than the proportion of non-NIH-funded articles (24.4%). Bibliometric influence measured by relative citation ratios was higher for NIH-funded (mean=14.78) than for non-NIH-funded (mean=5.07) articles. CONCLUSIONS: Study designs and funding supports varied widely across topics, but overall, NIH was the largest single funder of evidence informing 11 changed USPSTF I statements. Enhanced efforts by NIH and other stakeholders to address I statement evidence gaps are needed.

Safety and efficacy of HSP90 inhibitor ganetespib for neoadjuvant treatment of stage II/III breast cancer.

HSP90 inhibitors destabilize oncoproteins associated with cell cycle, angiogenesis, RAS-MAPK activity, histone modification, kinases and growth factors. We evaluated the HSP90-inhibitor ganetespib in combination with standard chemotherapy in patients with high-risk early-stage breast cancer. I-SPY2 is a multicenter, phase II adaptively randomized neoadjuvant (NAC) clinical trial enrolling patients with stage II-III breast cancer with tumors 2.5 cm or larger on the basis of hormone receptors (HR), HER2 and Mammaprint status. Multiple novel investigational agents plus standard chemotherapy are evaluated in parallel for the primary endpoint of pathologic complete response (pCR). Patients with HER2-negative breast cancer were eligible for randomization to ganetespib from October 2014 to October 2015. Of 233 women included in the final analysis, 140 were randomized to the standard NAC control; 93 were randomized to receive 150 mg/m2 ganetespib every 3 weeks with weekly paclitaxel over 12 weeks, followed by AC. Arms were balanced for hormone receptor status (51-52% HR-positive). Ganetespib did not graduate in any of the biomarker signatures studied before reaching maximum enrollment. Final estimated pCR rates were 26% vs. 18% HER2-negative, 38% vs. 22% HR-negative/HER2-negative, and 15% vs. 14% HR-positive/HER2-negative for ganetespib vs control, respectively. The predicted probability of success in phase 3 testing was 47% HER2-negative, 72% HR-negative/HER2-negative, and 19% HR-positive/HER2-negative. Ganetespib added to standard therapy is unlikely to yield substantially higher pCR rates in HER2-negative breast cancer compared to standard NAC, and neither HSP90 pathway nor replicative stress expression markers predicted response. HSP90 inhibitors remain of limited clinical interest in breast cancer, potentially in other clinical settings such as HER2-positive disease or in combination with anti-PD1 neoadjuvant chemotherapy in triple negative breast cancer.Trial registration: www.clinicaltrials.gov/ct2/show/NCT01042379.

New NIH Primary and Secondary Prevention Research During 2012-2019.

INTRODUCTION: This manuscript characterizes primary and secondary prevention research in humans and related methods research funded by NIH in 2012‒2019. METHODS: The NIH Office of Disease Prevention updated its prevention research taxonomy in 2019‒2020 and applied it to a sample of 14,523 new extramural projects awarded in 2012-2019. All projects were coded manually for rationale, exposures, outcomes, population focus, study design, and type of prevention research. All results are based on that manual coding. RESULTS: Taxonomy updates resulted in a slight increase, from an average of 16.7% to 17.6%, in the proportion of prevention research awards for 2012‒2017; there was a further increase to 20.7% in 2019. Most of the leading risk factors for death and disability in the U.S. were observed as an exposure or outcome in <5% of prevention research projects in 2019 (e.g., diet, 3.7%; tobacco, 3.9%; blood pressure, 2.8%; obesity, 4.4%). Analysis of existing data became more common (from 36% to 46.5%), whereas randomized interventions became less common (from 20.5% to 12.3%). Randomized interventions addressing a leading risk factor in a minority health or health disparities population were uncommon. CONCLUSIONS: The number of new NIH awards classified as prevention research increased to 20.7% in 2019. New projects continued to focus on observational studies and secondary data analysis in 2018 and 2019. Additional research is needed to develop and test new interventions or develop methods for the dissemination of existing interventions, which address the leading risk factors, particularly in minority health and health disparities populations.

Association of e-Cigarette Use With Discontinuation of Cigarette Smoking Among Adult Smokers Who Were Initially Never Planning to Quit.

Importance: Cigarette smokers not planning to quit are often overlooked in population studies evaluating the risk-benefit potential of electronic nicotine delivery products (e-cigarettes). Objective: To evaluate whether e-cigarette use is associated with discontinuing cigarette smoking among smokers who were initially never planning to quit. Design, Setting, and Participants: This cohort study used US nationally representative data from the longitudinal Population Assessment of Tobacco and Health Study (waves 2-5 conducted between October 2014 and November 2019), with participants evaluated in 3 pairs of interviews. Adult daily cigarette smokers initially not using e-cigarettes and with no plans to ever quit smoking for good (2489 observations from 1600 individuals) were included. Exposures: e-Cigarette use (ie, daily use, nondaily use, or no use) at follow-up interview among smokers not using e-cigarettes at baseline interview. Main Outcomes and Measures: The main outcomes were discontinuation of cigarette smoking (ie, no cigarette smoking) and discontinuation of daily cigarette smoking (ie, no daily cigarette smoking) at follow-up interview. Generalized estimating equations were used to evaluate the association between the exposure and each outcome, controlling for demographic characteristics and cigarettes smoked per day at baseline interview; all estimates were weighted. Results: The weighted population of adult daily cigarette smokers who were not using e-cigarettes and had no plans to ever quit smoking, based on data from 1600 participants, was 56.1% male (95% CI, 53.4%-58.7%), 10.1% Hispanic (95% CI, 8.2%-12.3%), 10.1% non-Hispanic Black (95% CI, 8.7%-11.7%), 75.6% non-Hispanic White (95% CI, 72.9%-78.2%), and 4.2% of other non-Hispanic race (95% CI, 3.3%-5.4%); 29.3% were aged 55 to 69 years (95% CI, 26.2%-32.6%), 8.9% were aged 70 years or older (95% CI, 6.8%-11.5%), 36.8% did not graduate from high school (95% CI, 34.1%-39.6%), 55.2% had an annual household income of less than $25 000 (95% CI, 52.3%-58.1%), 37.6% smoked 20 to 29 cigarettes per day (95% CI, 34.7%-40.6%), and 12.7% smoked 30 or more cigarettes per day (95% CI, 10.9%-14.7%). Overall, 6.2% of the population (95% CI, 5.0%-7.5%) discontinued cigarette smoking. Discontinuation rates were higher among those who used e-cigarettes daily (28.0%; 95% CI, 15.2%-45.9%) compared with not at all (5.8%; 95% CI, 4.7%-7.2%; adjusted odds ratio [aOR], 8.11; 95% CI, 3.14-20.97). Furthermore, 10.7% (95% CI, 9.1%-12.5%) discontinued daily cigarette smoking, with higher rates of discontinuation observed among those who used e-cigarettes daily (45.5%; 95% CI, 27.4%-64.9%) compared with not at all (9.9%; 95% CI, 8.2%-11.8%; aOR, 9.67; 95% CI, 4.02-23.25). Nondaily e-cigarette use was not associated with cigarette discontinuation (aOR, 0.53; 95% CI, 0.08-3.35) or daily cigarette discontinuation (aOR, 0.96; 95% CI, 0.44-2.09). Conclusions and Relevance: In this cohort study, daily e-cigarette use was associated with greater odds of cigarette discontinuation among smokers who initially had no plans to ever quit smoking. These findings support the consideration of smokers who are not planning to quit when evaluating the risk-benefit potential of e-cigarettes for smoking cessation in the population.