scholarly journals CTNI-51. NEUROCOGNITIVE FUNCTION (NCF) OUTCOMES OF RTOG FOUNDATION 3508: A PHASE 3 TRIAL OF ABT-414 WITH CONCURRENT CHEMORADIATION AND ADJUVANT TEMOZOLOMIDE IN PATIENTS WITH EGFR-AMPLIFIED NEWLY DIAGNOSED GBM

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii54-ii54
Author(s):  
Jeffrey S Wefel ◽  
Minhee Won ◽  
Andrew Lassman ◽  
Yaakov Stern ◽  
Tony Wang ◽  
...  

Abstract RTOG 3508/AbbVie M13-813/INTELLANCE-1 was a phase 3 trial of depatuximab-mafodotin (depatux-m, formerly ABT-414) that accrued 639 patients with EGFR-amplified newly diagnosed GBM. At the pre-specified interim OS analysis, the futility criteria were met and there was no survival benefit from adding depatux-m to SOC. Pre-specified secondary NCF analyses included time to decline in verbal learning and memory as assessed by the HVLT-R Total Recall based on the reliable change index. Exploratory NCF analyses examined changes in other HVLT-R outcomes over time. As corneal epitheliopathy causing visual impairment is a known toxicity of depatux-m, NCF tests that did not depend on visual acuity were employed. NCF testing occurred at baseline, day 1 of the first cycle of adjuvant depatux-m, every other cycle (i.e., 8 weeks) thereafter, and at progression. Compliance with test completion was 95% at screening and 80%, 70%, 58%, 51%, 47% thereafter through cycle 9. The most common reasons for missing data was site error. Time to HVLT-R Total Recall decline trended worse in the depatux-m arm compared to placebo but the difference was not significant (12 month deterioration: 41.2%, 95% CI: 3.50–47.2 vs 32.4%, 95% CI: 26.6- 38.4, p=0.052). The depatux-m arm, in comparison to the placebo arm, showed greater decline from baseline on the HVLT-R at the following time points: cycle 3 (Total Recall: mean= -1.8, SD=5.7 vs mean= -0.5, SD=5.5, respectively, p=0.046; Delayed Recall: mean= -1.1, SD=3.0 vs. mean= -0.2, SD=2.7, respectively, p=0.01), cycle 7 (Total Recall: mean= -0.6, SD=5.1 vs mean= 1.4, SD=5.0, respectively, p=0.009; Delayed Recall: mean -0.6, SD=3.0 vs. mean= 0.5, SD=2.7, respectively, p=0.01), and cycle 9 (Delayed Recall: mean=-0.4, SD=2.7 vs. mean= 0.8, SD=2.4, respectively, p=0.003). Depatux-m added to concurrent chemoradiation and adjuvant temozolomide was associated with faster time to deterioration and worse episodic learning and memory over time than placebo.

2020 ◽  
Author(s):  
Martin Klein ◽  
A Josephine Drijver ◽  
Martin J van den Bent ◽  
Jacolien C Bromberg ◽  
Khê Hoang-Xuan ◽  
...  

Abstract Background EORTC study 22033–26033 showed no difference in progression-free survival between high-risk low-grade glioma receiving either radiotherapy (RT) or temozolomide (TMZ) chemotherapy alone as primary treatment. Considering the potential long-term deleterious impact of RT on memory functioning, this study aims to determine whether TMZ is associated with less impaired memory functioning. Methods Using the Visual Verbal Learning Test (VVLT), memory functioning was evaluated at baseline and subsequently every 6 months. Minimal compliance for statistical analyses was set at 60%. Conventional indices of memory performance (VVLT Immediate Recall, Total Recall, Learning Capacity, and Delayed Recall) were used as outcome measures. Using a mixed linear model, memory functioning was compared between treatment arms and over time. Results Neuropsychological assessment was performed in 98 patients (53 RT, 46 TMZ). At 12 months, compliance had dropped to 66%, restricting analyses to baseline, 6 months, and 12 months. At baseline, patients in either treatment arm did not differ in memory functioning, sex, age, or educational level. Over time, patients in both arms showed improvement in Immediate Recall (P = 0.017) and total number of words recalled (Total Recall; P < 0.001, albeit with delayed improvement in RT patients (group by time; P = 0.011). Memory functioning was not associated with RT gross, clinical, or planned target volumes. Conclusion In patients with high-risk low-grade glioma there is no indication that in the first year after treatment, RT has a deleterious effect on memory function compared with TMZ chemotherapy.


2019 ◽  
Vol 25 (08) ◽  
pp. 834-844 ◽  
Author(s):  
Diego Rivera ◽  
Laiene Olabarrieta-Landa ◽  
Brian L. Brooks ◽  
Melissa M. Ertl ◽  
Itziar Benito-Sánchez ◽  
...  

AbstractObjective:To determine the prevalence of low scores for two neuropsychological tests with five total scores that evaluate learning and memory functions.Method:N = 5402 healthy adults from 11 countries in Latin America and the commonwealth of Puerto Rico were administered the Rey–Osterrieth Complex Figure (ROCF) and the Hopkins Verbal Learning Test (HVLT-R). Two-thirds of the participants were women, and the average age was 53.5 ± 20.0 years. Z-scores were calculated for ROCF Copy and Memory scores and HVLT-R Total Recall, Delayed Recall, and Recognition scores, adjusting for age, age2, sex, education, and interaction variables if significant for the given country. Each Z-score was converted to a percentile for each of the five subtest scores. Each participant was categorized based on his/her number of low scoring tests in specific percentile cutoff groups (25th, 16th, 10th, 5th, and 2nd).Results:Between 57.3% (El Salvador) and 64.6% (Bolivia) of the sample scored below the 25th percentile on at least one of the five scores. Between 27.1% (El Salvador) and 33.9% (Puerto Rico) scored below the 10th percentile on at least one of the five subtests. Between 5.9% (Chile, El Salvador, Peru) and 10.3% (Argentina) scored below the 2nd percentile on at least one of the five scores.Conclusions:Results are consistent with other studies that found that low scores are common when multiple neuropsychological outcomes are evaluated in healthy individuals. Clinicians should consider the higher probability of low scores when evaluating learning and memory using various sets of scores to reduce false-positive diagnoses of cognitive deficits.


1995 ◽  
Vol 22 (2) ◽  
pp. 157-164 ◽  
Author(s):  
Marja Äikiä ◽  
Reetta Kälviäinen ◽  
Paavo J. Riekkinen

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
E Zhao ◽  
NL Lowres ◽  
JT Tofler ◽  
SN Naismith ◽  
AB Baumman ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): the Vanguard Grant, Heart Foundation Background Cognitive impairment (CI) following acute coronary syndrome (ACS) is poorly understood. Purpose We aimed to explore the prevalence of CI in ACS patients four weeks post hospitalisation, the association with secondary prevention capacity and behaviours. Methods ACS inpatients who were free from visual deficits and dementia diagnoses were recruited. The post four weeks hospitalisation assessments included cognitive screening (Montreal Cognitive Assessment [MoCA], and Hopkins Verbal Learning Test [HVLT]), health literacy (Newest Vital Sign), depression (Patient Health Questionnaire-9), physical activity (Physical Activity Scale for the Elderly and Fitbit-Flex activity tracker), medication knowledge and adherence, sociodemographic and clinical factors. Results Participants (n = 45) had an average age of 65.07 ± 11.21 years, 82.2% were male, 64.4% were married/partnered and 82.2% had high school education or higher. CI occurred in 28.9% using either instrument, 20% using MoCA only and 15.6% using HVLT ­only. Cognitive domains affected were delayed recall (median = 5, range = 0-6) and new verbal learning and memory (15.6%). Adequate health literacy was less common in patients with CI (61.4%) than patients with normal cognition (90.3%, p = 0.024). Furthermore, patients with CI had trends for lower levels of secondary prevention capacity and behaviours, including fewer patients with high medication adherence, unlikely to be married or have an intimate partner, more depressive symptoms and lower levels of physical activity. Conclusions CI occurs in almost 30% of ACS patients four weeks post discharge, however a single screening tool is not sufficient to identify all cases. CI affected delayed recall, new verbal learning and memory; was associated with worse health literacy and may have potential implications for secondary prevention capacity.


2021 ◽  
Vol 12 ◽  
Author(s):  
Monica Bolocan ◽  
Claudia I. Iacob ◽  
Eugen Avram

We aimed to investigate the working memory (WM) and language separate contributions to verbal learning and memory in patients with unilateral drug-resistant temporal lobe epilepsy (drTLE); additionally, we explored the mediating role of WM on the relationship between the number of antiepileptic drugs (AEDs) and short-term verbal memory. We retrospectively enrolled 70 patients with left (LTLE; n = 44) and right (RTLE; n = 26) drTLE. About 40 similar (age and education) healthy controls were used to determine impairments of groups at WM, language (naming and verbal fluency), and verbal learning and memory (five trials list-learning, story memory—immediate recall). To disentangle the effect of learning from the short-term memory, we separately analyzed performances at the first trial, last trial, and delayed-recall list-learning measures, in addition to the total learning capacity (the sum of the five trials). Correlation and regression analyses were used to assess the contribution of potential predictors while controlling for main clinical and demographic variables, and ascertain the mediating role of WM. All patients were impaired at WM and story memory, whereas only LTLE showed language and verbal learning deficits. In RTLE, language was the unique predictor for the most verbal learning performances, whereas WM predicted the results at story memory. In LTLE, WM was the sole predictor for short-term verbal learning (list-learning capacity; trial 1) and mediated the interaction between AED number and the performance at these measures, whereas language predicted the delayed-recall. Finally, WM confounded the performance at short-term memory in both groups, although at different measures. WM is impaired in drTLE and contributes to verbal memory and learning deficits in addition to language, mediating the relationship between AED number and short-term verbal memory in LTLE. Clinicians should consider this overlap when interpreting poor performance at verbal learning and memory in drTLE.


2020 ◽  
Vol 26 (6) ◽  
pp. 607-623 ◽  
Author(s):  
Georgette D. Kanmogne ◽  
Julius Y. Fonsah ◽  
Anya Umlauf ◽  
Jacob Moul ◽  
Roland F. Doh ◽  
...  

AbstractObjective:There is lack of Cameroonian adult neuropsychological (NP) norms, limited knowledge concerning HIV-associated neurocognitive disorders in Sub-Saharan Africa, and evidence of differential inflammation and disease progression based on viral subtypes. In this study, we developed demographically corrected norms and assessed HIV and viral genotypes effects on attention/working memory (WM), learning, and memory.Method:We administered two tests of attention/WM [Paced Auditory Serial Addition Test (PASAT)-50, Wechsler Memory Scale (WMS)-III Spatial Span] and two tests of learning and memory [Brief Visuospatial Memory Test-Revised (BVMT-R), Hopkins Verbal Learning Test-Revised (HVLT-R)] to 347 HIV+ and 395 seronegative adult Cameroonians. We assessed the effects of viral factors on neurocognitive performance.Results:Compared to controls, people living with HIV (PLWH) had significantly lower T-scores on PASAT-50 and attention/WM summary scores, on HVLT-R total learning and learning summary scores, on HVLT-R delayed recall, BVMT-R delayed recall and memory summary scores. More PLWH had impairment in attention/WM, learning, and memory. Antiretroviral therapy (ART) and current immune status had no effect on T-scores. Compared to untreated cases with detectable viremia, untreated cases with undetectable viremia had significantly lower (worse) T-scores on BVMT-R total learning, BVMT-R delayed recall, and memory composite scores. Compared to PLWH infected with other subtypes (41.83%), those infected with HIV-1 CRF02_AG (58.17%) had higher (better) attention/WM T-scores.Conclusions:PLWH in Cameroon have impaired attention/WM, learning, and memory and those infected with CRF02_AG viruses showed reduced deficits in attention/WM. The first adult normative standards for assessing attention/WM, learning, and memory described, with equations for computing demographically adjusted T-scores, will facilitate future studies of diseases affecting cognitive function in Cameroonians.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS8587-TPS8587
Author(s):  
Andreas Rimner ◽  
W. Victoria Victoria Lai ◽  
Raffaele Califano ◽  
Salma K. Jabbour ◽  
Corinne Faivre-Finn ◽  
...  

TPS8587 Background: Concurrent chemoradiotherapy with etoposide and platinum (carboplatin/cisplatin) plus the anti‒PD-1 antibody pembrolizumab (pembro) has shown antitumor activity and acceptable safety in patients with limited-stage small-cell lung cancer (LS-SCLC). The poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib, has shown clinical activity in combination with checkpoint inhibitors in patients with SCLC. KEYLYNK-013 (NCT04624204) is a randomized, placebo-controlled, double-blind phase 3 trial of pembro plus concurrent chemoradiation therapy followed by pembro with or without olaparib in patients with newly diagnosed LS-SCLC. Methods: Eligible patients are those aged ≥18 years with previously untreated LS-SCLC, ECOG PS 0/1, and adequate pulmonary function. Patients are randomized 1:1:1 to receive pembro 200 mg Q3W (groups A and B) or pembro placebo (saline) Q3W (group C) during the chemoradiation phase. All patients also receive 4 cycles of chemotherapy (etoposide 100 mg/m2 on days 1, 2, and 3 of each cycle and investigator’s choice of carboplatin AUC 5 mg/mL/min or cisplatin 75 mg/m2 on day 1 of each cycle) with definitive thoracic radiotherapy (total dose of 45 Gy in 30 fractions twice daily over 3 weeks or 66 Gy in 33 fractions once daily over 6.5 weeks starting on day 1 of cycle 2). After chemoradiation, prophylactic cranial irradiation is strongly recommended for patients with CR/PR or at investigator’s discretion for patients with SD. Postchemoradiation patients receive pembro 400 mg Q6W plus olaparib placebo (group A), or pembro 400 mg Q6W plus olaparib 300 mg BID (group B), or pembro placebo plus olaparib placebo (group C) for 9 cycles/12 months. Randomization is stratified by ECOG PS (0 vs 1), SCLC stage (I/II vs III), radiation fractionation (twice vs once daily), and region (east Asia vs North America/western Europe/UK/Australia vs rest of world). Tumor imaging occurs at baseline, within 12 weeks of cycle 1 day 1, followed by Q9W to the end of year 2, Q12W in year 3, Q16W in year 4, every 6 months in year 5, and annually thereafter. Imaging is assessed per RECIST v1.1 by blinded independent central review. AEs are monitored from randomization to 30 days after cessation of study treatment (90 days for serious AEs) and graded per NCI-CTCAE v5.0. Health-related quality of life is assessed using EORTC-QLQ-C30 and QLQ-LC13. Primary endpoints are OS and PFS per RECIST v1.1 by blinded independent central review. OS and PFS are estimated by the Kaplan-Meier method. Between-group differences will be evaluated with stratified log-rank tests and Cox proportional hazard models with Efron’s method of tie handling. Secondary endpoints include ORR, duration of response, safety, and patient-reported outcomes. The study began enrollment in December 2020. Clinical trial information: NCT04624204.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Liane D. Heale ◽  
Kristin M. Houghton ◽  
Elham Rezaei ◽  
Adam D. G. Baxter-Jones ◽  
Susan M. Tupper ◽  
...  

Abstract Background Physical activity (PA) patterns in children with juvenile idiopathic arthritis (JIA) over time are not well described. The aim of this study was to describe associations of physical activity (PA) with disease activity, function, pain, and psychosocial stress in the 2 years following diagnosis in an inception cohort of children with juvenile idiopathic arthritis (JIA). Methods In 82 children with newly diagnosed JIA, PA levels, prospectively determined at enrollment, 12 and 24 months using the Physical Activity Questionnaire for Children (PAQ-C) and Adolescents (PAQ-A) raw scores, were evaluated in relation to disease activity as reflected by arthritis activity (Juvenile Arthritis Disease Activity Score (JADAS-71)), function, pain, and psychosocial stresses using a linear mixed model approach. Results in the JIA cohort were compared to normative Pediatric Bone Mineral Accrual Study data derived from healthy children using z-scores. Results At enrollment, PA z-score levels of study participants were lower than those in the normative population (median z-score − 0.356; p = 0.005). At enrollment, PA raw scores were negatively associated with the psychosocial domain of the Juvenile Arthritis Quality of Life Questionnaire (r = − 0.251; p = 0.023). There was a significant decline in PAQ-C/A raw scores from baseline (median and IQR: 2.6, 1.4–3.1) to 24 months (median and IQR: 2.1, 1.4–2.7; p = 0.003). The linear mixed-effect model showed that PAQ-C/A raw scores in children with JIA decreased as age, disease duration, and ESR increased. The PAQ-C/A raw scores of the participants was also negatively influenced by an increase in disease activity as measured by the JADAS-71 (p <  0.001). Conclusion Canadian children with newly diagnosed JIA have lower PA levels than healthy children. The decline in PA levels over time was associated with disease activity and higher disease-specific psychosocial stress.


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