Risk factors for neurocognitive impairment, emotional distress, and poor quality of life in survivors of pediatric rhabdomyosarcoma: A report from the Childhood Cancer Survivor Study.

BACKGROUND: Prevalence and risk of poor psychological outcomes following rhabdomyosarcoma (RMS) are not well-established. METHODS: Participants in this cross-sectional, case-control study (n = 713 survivors, 42.5% female; mean [SD] age, 30.5 [6.6] years; n = 706 siblings, 57.2% female; mean age, 32.8,[7.9] years) completed measures of neurocognition, emotional distress, and health-related quality of life (HRQOL). Multivariable logistic regression models identified treatments, health behaviors, and chronic conditions associated with impairment. RESULTS: Relative to siblings, more survivors reported neurocognitive impairment (task efficiency: 21.1% vs. 13.7%, emotional regulation: 16.7% vs. 11.0%, memory: 19.3% vs. 15.1%), elevated emotional distress (somatic distress: 12.9% vs. 4.7%, anxiety: 11.7% vs. 5.9%, depression: 22.8% vs. 16.9%) and poorer HRQOL (physical functioning: 11.1% vs. 2.8%, role functioning due to physical problems: 16.8% vs. 8.2%, pain: 17.5% vs. 10.0%, vitality: 22.3% vs. 13.8%, social functioning: 14.4% vs. 6.8%, emotional functioning: 17.1% vs. 10.6%). Cranial radiation increased risk for impaired task efficiency (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.14-4.63), whereas chest and pelvic radiation predicted increased risk of physical functioning (OR, 2.68; 95% CI, 1.16-6.21 and OR, 3.44; 95% CI, 1.70-6.95, respectively). Smoking was associated with impaired task efficiency (OR, 2.06; 95% CI, 1.14-3.70), memory (OR, 2.23; 95% CI, 1.26-3.95), anxiety (OR, 2.71; 95% CI, 1.36-5.41) and depression (OR, 1.77; 95% CI, 1.01-3.11). Neurologic conditions increased risk of anxiety (OR, 2.30; 95% CI, 1.04-5.10), and hearing conditions increased risk of depression (OR, 1.79; 95% CI, 1.05-3.03). Neurologic and hearing conditions, respectively, were associated with impaired memory (OR, 2.44; 95% CI, 1.20-4.95 and OR, 1.87; 95% CI, 1.05-3.35) and poor health perception (OR, 2.62; 95% CI, 1.62-1.28 and OR, 2.33; 95% CI, 1.34-4.06). CONCLUSIONS: RMS survivors are at significant risk for poor psychological outcomes. Advancing therapies for local control, smoking cessation, and managing chronic medical conditions may mitigate poor outcomes following RMS.

Neuro-oncology clinicians' perspectives on factors affecting brain cancer patients' access to medical assistance in dying: A qualitative study.

In most jurisdictions where medical assistance in dying (MAiD) is legal, patients must have decision-making capacity. Brain cancer often damages the cognitive networks required to maintain decision-making capacity. Using qualitative methodology guided by a relational ethics conceptual framework, this study explored neuro-oncology clinicians' perspectives on access to and eligibility for MAiD for patients diagnosed with brain cancer. We interviewed 24 neuro-oncology clinicians from 6 countries. Participants described the unique challenges facing brain cancer patients, potentially resulting in their inequitable access to MAiD. The findings highlight the importance of early end-of-life conversations, advance care planning, and access to end-of-life treatment options.

Long-term neurocognitive, psychological, and return to work outcomes in meningioma patients.

INTRODUCTION: This study aimed to investigate long-term neurocognitive, psychological, and return to work (RTW) outcomes in meningioma patients, and to explore whether neurocognitive and psychological factors influence RTW outcomes in this population. METHODS: In this retrospective study, 61 meningioma patients completed in-depth clinical neuropsychological assessments. Of these participants, 42 were of working-age and had RTW information available following neuropsychological assessment. Seventy-one percent and 80% of patients received radiation and surgery, respectively, with 49% receiving both radiation and surgery. Associations between demographic, medical, neurocognitive, psychological, and RTW data were analyzed using multivariable logistic regression analyses. RESULTS: In our sample, 68% of patients exhibited global neurocognitive impairment, with the largest effect sizes found on tests of visual memory (d = 0.73), executive function (d = 0.61), and attention (d = 0.54). Twenty-seven percent exhibited moderate to severe levels of depressive symptoms. In addition, 23% and 30% exhibited clinically significant state and trait anxiety, respectively. Forty-eight percent of patients were unable to RTW. Younger age, faster visuomotor processing speed, and, unexpectedly, higher trait anxiety scores were associated with an increased likelihood of returning to work. CONCLUSIONS: Meningioma patients are at risk of experiencing neurocognitive deficits, psychological symptoms, and difficulties returning to work. Our results suggest that neurocognitive and psychological factors contribute to RTW status in meningioma patients. Prospective research studies are necessary to increase our understanding of the complexity of functional disability in this growing population.

Neuro-Oncology Clinicians' Attitudes and Perspectives on Medical Assistance in Dying.

BACKGROUND: Medical assistance in dying (MAiD), also known as physician-assisted death, is currently legal in several locations across the globe. Brain cancer or its treatments can lead to cognitive impairment, which can impact decision-making capacity for MAiD. OBJECTIVE: We sought to explore neuro-oncology clinicians' attitudes and perspectives on MAiD, including interpretation of decision-making capacity for patient MAiD eligibility. METHODS: An online survey was distributed to members of national and international neuro-oncology societies. We asked questions about decision-making capacity and MAiD, in part using hypothetical patient scenarios. Multiple choice and free-text responses were captured. RESULTS: There were 125 survey respondents. Impaired cognition was identified as the most important factor that would signal a decline in patient capacity. At least 26% of survey respondents had moral objections to MAiD. Respondents thought that different hypothetical patients had capacity to make a decision about MAiD (range 18%-58%). In other hypothetical scenarios, fewer clinicians were willing to support a MAiD decision for a patient with an oligodendroglioma (26%) vs. glioblastoma (41%-70%, depending on the scenario). Time since diagnosis, performance status, and patient age seemed to affect support for MAiD decisions (Fisher's exact P-values 0.007, < 0.001, and 0.049, respectively). CONCLUSION: While there are differing opinions on the moral permissibility of MAiD in general and for neuro-oncology patients, most clinicians agree that capacity must be assessed carefully before a decision is made. End-of-life discussions should happen early, before the capacity is lost. Our results can inform assessments of patient capacity in jurisdictions where MAiD is legal.

A qualitative analysis of the benefits and barriers of support groups for patients with brain tumours and their caregivers.

PURPOSE: Brain tumours represent a significant burden for patients and caregivers. The aims of the present study were to explore the perceived benefits of support groups for patients and their caregivers, as well as the barriers to participation, and to generate suggestions for improvement. METHODS: Brain tumour patients and caregivers were recruited from the brain tumour centre at Princess Margaret Cancer Centre to participate in focus groups. Focus groups were audio-recorded, transcribed, and thematically analysed using qualitative methods. Eight patients (five who had attended the support groups and three who had not) and eight caregivers (all of whom attended the groups) participated in separate focus groups. RESULTS: Five major themes emerged: group cohesion (e.g., camaraderie and kinship), motivating factors to attend (e.g., loneliness), logistical factors that affected attendance (e.g., transportation), structure and content of the group (e.g., discussion topics), and suggestions for improvement (e.g., receiving personal reminders). CONCLUSIONS: This study highlights the supportive needs of brain tumour patients and their caregivers. The key findings provide helpful information on how to maximise the benefits of support groups for these populations.

The Impact of Brain Metastases and Associated Neurocognitive Aspects on Health Utility Scores in EGFR Mutated and ALK Rearranged NSCLC: A Real World Evidence Analysis.

BACKGROUND: In lung cancer, brain metastases (BM) and their treatment are associated with high economic burden and inferior health-related quality of life. In the era of targeted therapy, real world evidence through health utility scores (HUS) is critical for economic analyses. MATERIALS AND METHODS: In a prospective observational cohort study (2014-2016), outpatients with stage IV lung cancer completed demographic and EQ-5D-3L surveys (to derive HUS). Health states and clinicopathologic variables were obtained from chart abstraction. Patients were categorized by the presence or absence of BM; regression analyses identified factors that were associated with HUS. A subset of patients prospectively completed neurocognitive function (NCF) tests and/or the FACT-brain (FACT-Br) questionnaire, which were then correlated with HUS (Spearman coefficients; regression analyses). RESULTS: Of 519 patients with 1,686 EQ-5D-3L-derived HUS, 94 (18%) completed NCF tests and 107 (21%) completed FACT-Br; 301 (58%) never developed BM, 24 (5%) developed first BM during study period, and 194 (37%) had BM at study entry. The sample was enriched (46%) for EGFR mutations (EGFRm) and ALK-rearrangements (ALKr). There were no HUS differences by BM status overall and in subsets by demographics. In multivariable analyses, superior HUS was associated with having EGFRm/ALKr (p < .0001), no prior radiation for extracranial disease (p < .001), and both intracranial (p = .002) and extracranial disease control (p < .01). HUS correlated with multiple elements of the FACT-Br and tests of NCF. CONCLUSION: Having BM in lung cancer is not associated with inferior HUS in a population enriched for EGFRm and ALKr. Patients exhibiting disease control and those with oncogene-addicted tumors have superior HUS. IMPLICATIONS FOR PRACTICE: In the setting of EGFR mutations or ALK rearrangement non-small cell lung cancer (NSCLC), a diagnosis of brain metastases no longer consigns the patient to an inferior health state suggesting that new economic analyses in NSCLC are needed in the era of targeted therapies. Additionally, the EQ-5D questionnaire is associated with measures of health-related quality of life and neurocognitive scores suggesting this tool should be further explored in prospective clinical studies.

Cognitive rehabilitation for executive dysfunction in brain tumor patients: a pilot randomized controlled trial.

PURPOSE: Patients with brain tumors face unique quality of life challenges. Executive dysfunction is common and functionally limiting, with no established treatments as standard care. This pilot study evaluated the efficacy of Goal Management Training (GMT), a behavioral intervention combining mindfulness and strategy training, for improving executive and real-life functioning in this population. METHODS: Twenty-five primary brain tumor survivors were randomized to GMT, an active control (Brain Health Program, BHP), or a wait-list (WAIT) control group. The BHP was a supportive care intervention offering education and activities to promote general brain health, without cognitive strategy training. Participants in GMT and BHP completed eight individual sessions and homework between sessions; those in WAIT received usual care. Assessments at baseline, immediately post-training, and 4-month follow-up used a battery of objective and subjective measures, including functional goal attainment. RESULTS: Adherence (% sessions completed) was high for both GMT (98.9%) and BHP (84.4%). Executive functions improved with GMT but not BHP or WAIT (repeated measures analysis of variance, time-by-group interaction, post-training P = 0.077, follow-up P = 0.046). Both intervention groups reported fewer cognitive concerns at post-training (P = 0.049) and follow-up (P < 0.001). Functional goal attainment was greatest with GMT (post-training P = 0.027, follow-up P = 0.064). CONCLUSIONS: GMT improved executive and real-life functioning in brain tumor survivors, with gains maintained at 4-month follow-up. Clinical implementation of this adaptable program merits consideration for clinically stable patients with cognitive dysfunction. Further development and larger prospective cognitive rehabilitation trials appear warranted.

Sleep, emotional distress, and physical health in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.

OBJECTIVE: Sleep disorders are associated with psychological and physical health, although reports in long-term survivors of childhood cancer are limited. We characterized the prevalence and risk factors for behaviors consistent with sleep disorders in survivors and examined longitudinal associations with emotional distress and physical health outcomes. METHODS: Survivors (n = 1933; median [IQR] age = 35 [30, 41]) and siblings (n = 380; age = 33 [27, 40]) from the Childhood Cancer Survivor Study completed measures of sleep quality, fatigue, and sleepiness. Emotional distress and physical health outcomes were assessed approximately 5 years before and after the sleep survey. Multivariable logistic or modified Poisson regression models examined associations with cancer diagnosis, treatment exposures, and emotional and physical health outcomes. RESULTS: Survivors were more likely to report poor sleep efficiency (30.8% vs 24.7%; prevalence ratio [PR] = 1.26; 95% confidence interval, 1.04-1.53), daytime sleepiness (18.7% vs 14.2%; PR = 1.31 [1.01-1.71]), and sleep supplement use (13.5% vs 8.3%; PR = 1.56 [1.09-2.22]) than siblings. Survivors who developed emotional distress were more likely to report poor sleep efficiency (PR = 1.70 [1.40-2.07]), restricted sleep time (PR = 1.35 [1.12-1.62]), fatigue (PR = 2.11 [1.92-2.32]), daytime sleepiness (PR = 2.19 [1.71-2.82]), snoring (PR = 1.85 [1.08-3.16]), and more sleep medication (PR = 2.86 [2.00-4.09]) and supplement use (PR = 1.89[1.33-2.69]). Survivors reporting symptoms of insomnia (PR = 1.46 [1.02-2.08]), fatigue (PR = 1.31 [1.01-1.72]), and using sleep medications (PR = 2.16 [1.13-4.12]) were more likely to develop migraines/headaches. CONCLUSIONS: Survivors report more sleep difficulties and efforts to manage sleep than siblings. These sleep behaviors are related to worsening or persistently elevated emotional distress and may result in increased risk for migraines. Behavioral interventions targeting sleep may be important for improving health outcomes.

Cognitive rehabilitation for cancer-related cognitive dysfunction: a systematic review.

PURPOSE: Individuals with non-central nervous system (CNS) cancers can experience cancer-related cognitive dysfunction (CRCD), negatively impacting daily functioning and quality of life. This systematic review examined cognitive rehabilitation programs aimed at improving cognitive function. METHODS: PsychInfo and PubMed were searched in February 2019. Eligible studies evaluated a cognitive rehabilitation program for adults with non-CNS cancers and included at least one objective cognitive measure. Across studies, we assessed methodological quality using relevant criteria based on published intervention-related review guidelines and examined findings from performance-based and self-reported outcome measures. RESULTS: 19 studies met inclusion criteria, totalling 1124 participants altogether. These studies included randomized controlled trials (n = 12), partial, quasi or non-randomized controlled trials (n = 3) and single-arm pilot studies (n = 4). All studies found improvements on at least one cognitive measure (performance-based or self-reported). By cognitive domain, objective improvements in memory were most commonly reported, followed by executive functions and processing speed. In terms of methodological quality, studies generally provided clear descriptions of participants and interventions. However, limitations included lack of standardized terminology for interventions, discrepancies in outcome measures, and incomplete statistical reporting. CONCLUSIONS: The available evidence supports clinical implementation of cognitive rehabilitation to improve CRCD, with further work in program development, dissemination, and feasibility recommended. We provide specific recommendations to facilitate future research and integration in this field.

Comorbid symptoms of emotional distress in adult survivors of childhood cancer.

BACKGROUND: Childhood cancer survivors are at risk for emotional distress symptoms, but symptom comorbidity has not been previously examined. This study examined distress profiles for adult survivors of childhood cancer diagnosed between 1970 and 1999. METHODS: Self-reported depression, anxiety, and somatization symptoms from Brief Symptom Inventory 18 were examined in survivors (n = 16,079) and siblings (n = 3085) from the Childhood Cancer Survivor Study. A latent profile analysis identified clusters of survivors with individual and comorbid symptoms. Disease, treatment, and demographic predictors of distress comorbidity patterns were examined with multinomial logistic regressions. RESULTS: Four clinically relevant profiles were identified: low distress on all subscales (asymptomatic, 62%), high distress on all subscales (comorbid distress, 11%), elevated somatization (somatic symptoms, 13%), and elevated depression and anxiety (affective distress, 14%). Compared with siblings, fewer survivors were asymptomatic (62% vs 74%, P < .0001), and more had comorbid distress (11% vs 5%, P < .0001). Survivors of leukemia (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.12-1.61), central nervous system tumors (OR, 1.30; 95% CI, 1.05-1.61), and sarcoma (OR, 1.26; 95% CI, 1.01-1.57) had a greater risk of comorbid distress than survivors of solid tumors. Psychoactive medications were associated with comorbid distress (P < .0001), and this suggested that this group was refractory to traditional medical management. Comorbid distress was associated with poor perceived health (OR, 31.7; 95% CI, 23.1-43.3), headaches (OR, 3.2; 95% CI, 2.8-3.7), and bodily pain (OR, 4.0; 95% CI, 3.2-5.0). CONCLUSIONS: A significant proportion of survivors are at risk for comorbid distress, which may require extensive treatment approaches beyond those used for individual symptoms. Cancer 2016;122:3215-24. © 2016 American Cancer Society.

Illness intrusiveness and subjective well-being in patients with glioblastoma.

Glioblastoma (GBM) is the most common adult CNS malignancy but its impact on quality of life (QOL) is poorly understood. In other patient populations, illness intrusiveness (the extent to which disease and treatment disrupts valued activities and interests) is associated with low subjective well-being, after controlling for disease and treatment variables. In this cross-sectional cohort study, we examined the relations among illness intrusiveness, disease burden, and subjective well-being in GBM. 73 GBM patients completed validated self-report measures of depression, positive affect, illness intrusiveness, and health-related QOL. Responses were compared to data from six other cancer groups using repeated measures analyses of variance. Hierarchical multiple-regression analyses tested the hypothesis that illness intrusiveness accounts for well-being after controlling for the effects of disease burden. GBM patients reported less positive affect, more depression, and more illness intrusiveness than people with other cancers. Illness intrusiveness correlated with depression and (low) positive affect. Associations among cancer symptoms, depression, and positive affect decreased when illness intrusiveness was added to regression equations. Good performance status and high cancer-symptom burden were associated with illness intrusiveness and depression. GBM patients report greater distress, lower positive affect, and more illness intrusiveness than people with other cancers. Subjective well-being is mediated in part by illness intrusiveness in this population. In addition to medical treatment, efforts to help patients remain engaged in valued activities and interests may help preserve QOL after the diagnosis of a GBM.

Together and apart: providing psychosocial support for patients and families living with brain tumors.

PURPOSE: Brain tumors are associated with neurological sequelae and poor survival, contributing to distress in patients and their families. Our institution has conducted separate support groups for brain tumor patients and caregivers since 1999. This retrospective cohort study aimed to identify characteristics of brain tumor group participants in relation to attendance frequency, and compare themes of discussion in patient and caregiver groups. METHODS: Demographic and medical characteristics were obtained from patient and caregiver group registration sheets and medical chart review. We quantified discussion topics recorded by group facilitators between 1999 and 2006, extracted themes, and examined similarities and differences in the way these themes were expressed. RESULTS: A total of 137 patients and 238 caregivers attended the groups; about half attended more than one session. The chart review of a randomly selected subset of patient participants revealed that 57.5 % were married, 58.8 % had high-grade gliomas, and 55 % attended their first group within 3 months of diagnosis or at tumor progression. Both groups discussed physical and cognitive consequences, emotional reactions, relationships, coping, end of life, and practical issues. Caregivers discussed difficulties achieving self-care and caregiver burden. CONCLUSIONS: Brain tumor support group facilitators can expect to encounter a range of medical and psychosocial issues in accommodating patients' and caregivers' diverse concerns. Separate brain tumor patient and caregiver groups may allow participants to explore those concerns without worrying about effects on their friends or family. It remains to be seen whether the groups meet the needs of attendees, and whether those who do not attend the groups have unmet needs.

Long-term neurocognitive and psychological outcomes in meningioma survivors: Individual changes over time and radiation dosimetry.

Background: This study investigates long-term changes in neurocognitive performance and psychological symptoms in meningioma survivors and associations with radiation dose to circumscribed brain regions. Methods: We undertook a retrospective study of meningioma survivors who underwent longitudinal clinical neurocognitive assessments. Change in neurocognitive performance or psychological symptoms was assessed using reliable change indices. Radiation dosimetry, if prescribed, was evaluated based on treatment-planning computerized tomography co-registered with contrast-enhanced 3D T1-weighted magnetic resonance imaging. Mixed effects analyses were used to explore whether incidental radiation to brain regions outside the tumor influences neurocognitive and psychological outcomes. Results: Most (range = 41%-93%) survivors demonstrated stable-albeit often below average-neurocognitive and psychological trajectories, although some also exhibited improvements (range = 0%-31%) or declines (range = 0%-36%) over time. Higher radiation dose to the parietal-occipital region (partial R2 = 0.462) and cerebellum (partial R2 = 0.276) was independently associated with slower visuomotor processing speed. Higher dose to the hippocampi was associated with increases in depression (partial R2 = 0.367) and trait anxiety (partial R2 = 0.236). Conclusions: Meningioma survivors experience neurocognitive deficits and psychological symptoms many years after diagnosis, and a proportion of them decline over time. This study offers proof of concept that incidental radiation to brain regions beyond the tumor site may contribute to these sequelae. Future investigations should include radiation dosimetry when examining risk factors that contribute to the quality of survivorship in this growing population.

Assessing information and service needs of young adults with cancer at a single institution: the importance of information on cancer diagnosis, fertility preservation, diet, and exercise.

BACKGROUND: Young adults (YA) with cancer have unique psychosocial and medical needs. The objective of this study was to identify information and service needs important to YA cancer patients. METHODS: A supportive care needs survey was administered to ambulatory patients (

Psychosocial challenges and resource needs of young adult cancer survivors: implications for program development.

Young adult (YA) cancer survivors have specific needs because of their age and life stage. The authors investigated the challenges and resource needs of YA survivors, exploring the influence of age at diagnosis (i.e., diagnosis during childhood vs. young adulthood) and the diagnosis of a brain tumor. The authors conducted four focus groups with YA survivors (N = 22, age 18-35), treated for brain tumors or other cancers in childhood (mean age at diagnosis ± SD: brain, 10.7 ± 2.86; other cancers, 10.5 ± 3.51) or as YAs (brain, 23.5 ± 4.04; other cancers, 25.6 ± 4.10). Transcripts of audiotaped sessions were coded using thematic analysis. Common challenges across the groups included physical appearance, fertility, late effects, social relationships, and changing priorities. Childhood cancer survivors struggled with identity formation, social isolation, and health care transitions. Concerns specific to survivors diagnosed as YAs included financial independence and protecting parents. Childhood brain tumor survivors struggled with cognitive deficits, limited career options, and poor social skills, whereas brain tumor survivors diagnosed as YAs emphasized cognitive decline, loss of autonomy, and living with an incurable disease. Despite the unique challenges identified, all groups described similar resource needs including peer support, age-specific information, and having health care providers proactively raise salient issues. Young adult cancer survivors have many similar psychosocial and information needs regardless of age at or type of diagnosis that differ from those of pediatric and older adult survivors. With improved survival rates, the small number of YA in any one institution will grow. It will become increasingly important to create comprehensive, age-appropriate YA programs that address overlapping and unique needs of survivors at this life stage.

Measuring what gets done: Using goal attainment scaling in a vocational counseling program for survivors of childhood cancer.

BACKGROUND: Childhood cancer survivors face education and employment challenges due to physical, cognitive, and psychosocial effects of the disease and treatments, with few established programs to assist them. The objectives of this study were to describe the implementation of Goal Attainment Scaling (GAS) to evaluate an educational and vocational counseling program established for survivors of childhood cancer, and analyze patterns of program engagement and client outcomes, stratified by demographic and diagnostic characteristics. METHODS: A population-based retrospective cohort study of childhood cancer survivors who were engaged with the Pediatric Oncology Group of Ontario's School and Work Transitions Program (SWTP) between January 2015 and December 2018 was utilized. Survivors were followed from SWTP engagement until May 30, 2019 to capture goal attainment. Individual goals were summarized across various demographic, disease, and treatment strata. RESULTS: In total, 470 childhood cancer survivors (median age = 17.9, 58% male) set 4,208 goals in the SWTP during the study period. The mean length of observation was 130.8 weeks (SD = 56.9). Overall, 68% of the goals were achieved. Eighty-three percent of the goals related to further education. Clients diagnosed with a solid tumor set the most goals on average, followed by those with central nervous system tumors and leukemia/lymphoma. CONCLUSIONS: The SWTP assists childhood cancer survivors in realizing their academic and vocational goals. Application of GAS in this setting is a feasible way to evaluate program outcomes. From the volume and breadth of the GAS goals set and achieved, the overall success of the SWTP appears strong.

Neurocognitive impairment, neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms in patients with newly diagnosed glioblastoma.

Background: In addition to poor survival rates, individuals with glioblastoma (GBM) are at risk of neurocognitive impairment due to multiple factors. This study aimed to characterize neurocognitive impairment, neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms in newly diagnosed GBM patients; and to examine whether neurobehavioral symptoms, fatigue, sleep, and depressive symptoms influence neurocognitive performance. Methods: This study was part of a prospective, inception cohort, single-arm exercise intervention in which GBM patients underwent a neuropsychological assessment shortly after diagnosis (median 4 weeks; ie, baseline) and 3, 6, 12, and 18 months later, or until tumor progression. Here, we present baseline data. Forty-five GBM patients (mean age = 55 years) completed objective neurocognitive tests, and self-report measures of neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms. Results: Compared to normative samples, GBM patients scored significantly lower on all neurocognitive tests, with 34 (76%) patients exhibiting neurocognitive impairment. Specifically, 53% exhibited impairment in memory retention, 51% in executive function, 42% in immediate recall, 41% in verbal fluency, and 24% in attention. There were high rates of clinically elevated sleep disturbance (70%), fatigue (57%), depressive symptoms (16%), and neurobehavioral symptoms (27%). A multivariate regression analysis revealed that depressive symptoms are significantly associated with neurocognitive impairment. Conclusions: GBM patients are vulnerable to adverse outcomes including neurocognitive impairment, neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms shortly after diagnosis, prior to completing chemoradiation. Those with increased depressive symptoms are more likely to demonstrate neurocognitive impairment, highlighting the need for early identification and treatment of depression in this population.

Late-onset Cognitive Impairment and Modifiable Risk Factors in Adult Childhood Cancer Survivors.

Importance: Long-term survivors of childhood cancer may be at elevated risk for new neurocognitive impairment and decline as they age into adulthood. Objective: To determine whether aging adult childhood cancer survivors report more new-onset neurocognitive impairments compared with their siblings and to identify risk factors associated with such impairments. Design, Setting, and Participants: Participants of this cohort study included adult survivors of childhood cancer from the Childhood Cancer Survivor Study and their siblings as a control group. The original cohort included survivors who received a diagnosis between January 1, 1970, and December 31, 1986, for whom longitudinal neurocognitive assessment was available. This study examined the prevalence of new-onset neurocognitive impairment between baseline (23.4 years after diagnosis) and follow-up (35.0 years after diagnosis). The analysis was performed from January 2021 to May 2022. Exposures: Cancer treatment exposures were abstracted from medical records. Chronic health conditions were graded using Common Terminology Criteria for Adverse Events version 4.03. Main Outcomes and Measures: The primary outcome was new-onset (present at follow-up, but not present at baseline) neurocognitive impairment (defined as a score in the worst 10% of the sibling cohort). Impairment was assessed using the Childhood Cancer Survivor Study Neurocognitive questionnaire. Relative risks (RRs) and 95% CIs were used to estimate associations of neurocognitive impairment with treatment and health behaviors and conditions using generalized linear models. Results: The cohort comprised 2375 survivors (mean [SD] age at evaluation, 31.8 [7.5] years; 1298 women [54.6%]) of childhood cancer, including acute lymphoblastic leukemia (ALL; 1316 participants), central nervous system (CNS) tumors (488 participants), and Hodgkin lymphoma (HL; 571 participants). A total of 232 siblings (mean [SD] age at evaluation, 34.2 [8.4] years; 134 women [57.8%]) were included. Compared with siblings, a higher proportion of survivors with no impairment in memory at baseline had new-onset memory impairment at follow-up: siblings proportion, 7.8% (95% CI, 4.3%-11.4%); ALL survivors treated with chemotherapy only, 14.0% (95% CI, 10.7%-17.4%); ALL survivors treated with cranial radiation (CRT), 25.8% (95% CI, 22.6%-29.0%); CNS tumor survivors, 34.7% (95% CI, 30.0%-39.5%); and HL survivors, 16.6% (95% CI, 13.4%-19.8%). New-onset memory impairment was associated with CRT in CNS tumor survivors (RR, 1.97; 95% CI, 1.33-2.90) and alkylator chemotherapy greater than or equal to 8000 mg/m2 in ALL survivors treated without CRT (RR, 2.80; 95% CI, 1.28-6.12). Neurologic conditions mediated the impact of CRT on new-onset memory impairment in CNS survivors. Smoking, low educational attainment, and low physical activity were associated with elevated risk for new-onset memory impairment. Conclusions and Relevance: These findings suggest that adult survivors of childhood cancer are at elevated risk for late-onset memory impairment related to modifiable risk factors identified early in survivorship.

Radiation dose to circumscribed brain regions and neurocognitive function in patients with meningioma.

Background: Although radiation (RT) is standard treatment for many brain tumors, it may contribute to neurocognitive decline. The objective of this study was to investigate associations between RT dose to circumscribed brain regions and specific neurocognitive domains in patients with meningioma. Methods: We undertook a retrospective study of 40 patients with meningioma who received RT and underwent an in-depth clinical neurocognitive assessment. Radiation dosimetry characteristics were delineated based on treatment planning computerized tomography co-registered with contrast-enhanced 3D T1-weighted magnetic resonance imaging. Principal components analysis was applied to organize neurocognitive test scores into factors, and multivariate multiple linear regression models were undertaken to examine if RT dose to circumscribed brain regions is associated with specific neurocognitive outcomes. Results: Radiation dose to brain regions was associated with neurocognitive functions across a number of domains. High dose to the parietal-occipital region was associated with slower visuomotor processing speed (mean dose, ß = -1.100, P = .017; dose to 50% of the region [D50], ß = -0.697, P = .049). In contrast, high dose to the dorsal frontal region was associated with faster visuomotor processing speed (mean dose, ß = 0.001, P = .036). Conclusions: These findings suggest that RT delivered to brain regions (ie, parietal-occipital areas) may contribute to poor neurocognitive outcomes. Given that modern radiotherapy techniques allow for precise targeting of dose delivered to brain regions, prospective trials examining relations between dose and neurocognitive functions are warranted to confirm these preliminary results.

Factors associated with cognitive impairment and cognitive concerns in patients with metastatic non-small cell lung cancer.

BACKGROUND: Knowledge regarding cognitive problems in metastatic non-small cell lung cancer (mNSCLC) is limited. Such problems may include both patient-reported cognitive concerns and demonstrable cognitive impairment. Greater understanding of these outcomes is needed to inform rehabilitation strategies for these difficulties. We aimed to identify the frequency of cognitive problems and associated factors in patients with mNSCLC. METHODS: In this cross-sectional study, adults with mNSCLC completed validated neuropsychological tests and self-report questionnaires measuring cognitive concerns, neurobehavioral concerns, depression, demoralization, illness intrusiveness, self-esteem, and physical symptoms. Cognitive impairment (performance based) was defined according to International Cancer and Cognition Task Force criteria. Clinically significant cognitive concerns were defined by a score ≥1.5 SD below the normative mean on the Functional Assessment of Cancer Therapy-Cognitive Function Perceived Cognitive Impairment (FACT-Cog PCI). Univariate and multivariate logistic regression analyses were performed to identify associated factors. RESULTS: Of 238 patients approached, 77 participated (median age: 62 years; range: 37-82). Brain metastases were present in 41 patients (53%), and 23 (29%) received cranial irradiation. Cognitive impairment and cognitive concerns were present in 31 (40%) and 20 patients (26%), respectively. Cognitive impairment and cognitive concerns co-occurred in 10 patients (13%), but their severity was unrelated. Cognitive impairment was associated with cranial irradiation (odds ratio [OR] = 2.89; P = .04), whereas cognitive concerns were associated with greater illness intrusiveness (OR = 1.04; P = .03) and lower self-esteem (OR = 0.86; P = .03). CONCLUSIONS: Cognitive impairment and cognitive concerns are both common in patients with mNSCLC but are not necessarily related, and their risk factors differ. The association of illness intrusiveness and self-esteem with cognitive concerns can inform therapeutic interventions in this population.