NCCN Guidelines® Insights: Survivorship, Version 1.2023.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals address the complex and varied needs of cancer survivors. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for psychosocial and physical problems resulting from adult-onset cancer and its treatment; recommendations to help promote healthy behaviors and immunizations in survivors; and a framework for care coordination. These NCCN Guidelines Insights summarize recent guideline updates and panel discussions pertaining to sleep disorders, fatigue, and cognitive function in cancer survivors.

IMPACT the Brain: A Team-Based Approach to Management of Metastatic Breast Cancer With CNS Metastases.

PURPOSE: CNS metastases are associated with decreased survival and quality of life for patients with metastatic breast cancer (MBC). Team-based care can optimize outcomes. IMPACT the Brain is a care coordination program that aims to improve access to team-based care for patients with MBC and CNS metastases. MATERIALS AND METHODS: Patients with MBC and CNS metastases were eligible for enrollment in this care coordination program. A team of specialists supported a dedicated program coordinator who provided navigation, education, specialty referral, and clinical trial screening. A unique intake form developed for the program created personalized, coordinated, and expedited specialty referrals. Patient-reported outcomes and caregiver burden assessments were collected on a voluntary basis throughout enrollment. Data were analyzed using descriptive statistics. RESULTS: Sixty patients were referred, and 53 were enrolled (88%). The median time to program enrollment was 1 day (range, 0-11) and to first visit was 5 days (range, 0-25). On the basis of the program intake form, 47 referrals were made across six specialties, most commonly physical medicine and rehabilitation (n = 10), radiation oncology (n = 10), and neuropsychology (n = 10). Nineteen patients (36%) consented to enroll in clinical trials. CONCLUSION: A tailored team-based care coordination program for patients with MBC and CNS metastases is feasible. Use of a unique intake screening form by a dedicated program coordinator resulted in faster time to first patient visit, enabled access to subspecialist care, and supported enrollment in clinical trials. Future research should focus on intervention development using PRO data collected in this care coordination program.

Exercise improves health-related quality of life sleep and fatigue domains in adult high- and low-grade glioma patients.

PURPOSE: The impact of exercise on health-related quality of life (HRQOL) in patients with glioma remains unknown. We hypothesized that glioma patients with low exercise tolerance experience more distress in HRQOL sleep and fatigue domains than patients with high tolerance to exercise. METHODS: Thirty-eight male and female patients with low- or high-grade glioma treated at a single tertiary care institution participated. Patients completed a validated telephone survey to determine their exercise habits before and following diagnosis. An unpaired t-test was run to measure the interaction between exercise tolerances on HRQOL functional and impairment domains. RESULTS: Those with low pre-morbid physical activity levels had more distress in HRQOL sleep and fatigue domains. The effects were independent of plasma brain-derived neurotrophic factor (BDNF) levels and the degree of exercise did not appear to impact plasma BDNF in adult glioma patients. CONCLUSIONS: The aim of this study was to examine the significance of exercise habits on perioperative functional outcomes in patients with low-grade or high-grade glioma. We found that glioma patients with low tolerance to exercise had more sleep disturbances and greater fatigue than glioma patients with high tolerance to exercise. Furthermore, exercise tolerance in the adult glioma population does not appear to impact plasma BDNF secretion.

A Phase 2 Study of Dose-intensified Chemoradiation Using Biologically Based Target Volume Definition in Patients With Newly Diagnosed Glioblastoma.

PURPOSE: We hypothesized that dose-intensified chemoradiation therapy targeting adversely prognostic hypercellular (TVHCV) and hyperperfused (TVCBV) tumor volumes would improve outcomes in patients with glioblastoma. METHODS AND MATERIALS: This single-arm, phase 2 trial enrolled adult patients with newly diagnosed glioblastoma. Patients with a TVHCV/TVCBV >1 cm3, identified using high b-value diffusion-weighted magnetic resonance imaging (MRI) and dynamic contrast-enhanced perfusion MRI, were treated over 30 fractions to 75 Gy to the TVHCV/TVCBV with temozolomide. The primary objective was to estimate improvement in 12-month overall survival (OS) versus historical control. Secondary objectives included evaluating the effect of 3-month TVHCV/TVCBV reduction on OS using Cox proportional-hazard regression and characterizing coverage (95% isodose line) of metabolic tumor volumes identified using correlative 11C-methionine positron emission tomography. Clinically meaningful change was assessed for quality of life by the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire C30, for symptom burden by the MD Anderson Symptom Inventory for brain tumor, and for neurocognitive function (NCF) by the Controlled Oral Word Association Test, the Trail Making Test, parts A and B, and the Hopkins Verbal Learning Test-Revised. RESULTS: Between 2016 and 2018, 26 patients were enrolled. Initial patients were boosted to TVHCV alone, and 13 patients were boosted to both TVHCV/TVCBV. Gross or subtotal resection was performed in 87% of patients; 22% were O6-methylguanine-DNA methyltransferase (MGMT) methylated. With 26-month follow-up (95% CI, 19-not reached), the 12-month OS rate among patients boosted to the combined TVHCV/TVCBV was 92% (95% CI, 78%-100%; P = .03) and the median OS was 20 months (95% CI, 18-not reached); the median OS for the whole study cohort was 20 months (95% CI, 14-29 months). Patients whose 3-month TVHCV/TVCBV decreased to less than the median volume (3 cm3) had superior OS (29 vs 12 months; P = .02). Only 5 patients had central or in-field failures, and 93% (interquartile range, 59%-100%) of the 11C-methionine metabolic tumor volumes received high-dose coverage. Late grade 3 neurologic toxicity occurred in 2 patients. Among non-progressing patients, 1-month and 7-month deterioration in quality of life, symptoms, and NCF were similar in incidence to standard therapy. CONCLUSIONS: Dose intensification against hypercellular/hyperperfused tumor regions in glioblastoma yields promising OS with favorable outcomes for NCF, symptom burden, and quality of life, particularly among patients with greater tumor reduction 3 months after radiation therapy.

BDNF, COMT, and DRD2 polymorphisms and ability to return to work in adult patients with low- and high-grade glioma.

BACKGROUND: Cognitive and language dysfunction is common among patients with glioma and has a significant impact on survival and health-related quality of life (HRQOL). Little is known about the factors that make individual patients more or less susceptible to the cognitive sequelae of the disease. A better understanding of the individual and population characteristics related to cognitive function in glioma patients is required to appropriately stratify patients, prognosticate, and develop more efficacious treatment regimens. There is evidence that allelic variation among genes involved in neurotransmission and synaptic plasticity are related to neurocognitive performance in states of health and neurologic disease. METHODS: We studied the association of single-nucleotide polymorphism variations in brain-derived neurotrophic factor (BDNF, rs6265), dopamine receptor 2 (DRD2, rs1076560), and catechol-O-methyltransferase (COMT, rs4680) with neurocognitive function and ability to return to work in glioma patients at diagnosis and at 3 months. We developed a functional score based on the number of high-performance alleles that correlates with the capacity for patients to return to work. RESULTS: Patients with higher-performing alleles have better scores on neurocognitive testing with the Repeatable Battery for the Assessment of Neuropsychological Status and Stroop test, but not the Trail Making Test. CONCLUSIONS: A better understanding of the genetic contributors to neurocognitive performance in glioma patients and capacity for functional recovery is necessary to develop improved treatment strategies based on patient-specific factors.

Montreal Cognitive Assessment as a screening tool: Influence of performance and symptom validity.

BACKGROUND: We evaluated Montreal Cognitive Assessment (MoCA) performance in a veteran traumatic brain injury (TBI) population, considering performance validity test (PVT) and symptom validity test (SVT) data, and explored associations of MoCA performance with neuropsychological test performance and self-reported distress. METHODS: Of 198 consecutively referred veterans to a Veterans Administration TBI/Polytrauma Clinic, 117 were included in the final sample. The MoCA was administered as part of the evaluation. Commonly used measures of neuropsychological functioning and performance and symptom validity were also administered to aid in diagnosis. RESULTS: Successively worse MoCA performances were associated with a greater number of PVT failures (ps < 0.05). Failure of both the SVT and at least 1 PVT yielded the lowest MoCA scores. Self-reported distress (both posttraumatic stress disorder symptoms and neurobehavioral cognitive symptoms) was also related to MoCA performance. CONCLUSIONS: Performance on the MoCA is influenced by task engagement and symptom validity. Causal inferences about neurologic and neurocognitive impairment, particularly in the context of mild TBI, wherein the natural course of recovery is well known, should therefore be made cautiously when such inferences are based heavily on MoCA scores. Neuropsychologists are well versed in the assessment of performance and symptom validity and thus may be well suited to explore the influences of abnormal performances on cognitive screening.

Health Related Quality of Life in Adult Low and High-Grade Glioma Patients Using the National Institutes of Health Patient Reported Outcomes Measurement Information System (PROMIS) and Neuro-QOL Assessments.

Health related quality of life (HRQOL) measures have become increasingly important in the management of glioma patients in both research and clinical practice settings. Functional impairment is common in low-grade and high-grade glioma patients as the disease has both oncological and neurological manifestations. Natural disease history as well as medical or surgical treatment can negatively influence HRQOL. There are no universal standards for HRQOL assessment in glioma patients. In this study, we examine patient perspectives on functional outcome domains and report the prevalence of impairments rates using the National Institutes of Health (NIH) Patient Reported Outcomes Measurement Information System (PROMIS) and Neuro-QOL item banks as measures of HRQOL. Retrospective analysis of a prospectively collected dataset involving 79 glioma patients reveals that quality of life concerns are the most important consideration behind making decisions about treatment in 80.7% of patients. The prevalence of functional impairment by PROMIS and NEURO-QOL assessment is high, ranging from 28.6% in the physical function domain to 43.9% in the cognitive function domain. Pain and anxiety related to physical decline is higher in LGG patients compared to HGG patients. Aphasia severity also impacts HRQOL. The results of this study suggest that the PROMIS and NEURO-QOL assessments may be important HRQOL metrics for future use in larger clinical research and clinical trial settings.

Suspiciously slow: timed digit span as an embedded performance validity measure in a sample of veterans with mTBI.

OBJECTIVE: To explore the utility of Timed Digit Span (TDS) as an embedded performance validity test (PVT) in a sample of veterans with mild traumatic brain injury (mTBI). We hypothesize that TDS will predict PVT failure on an established stand-alone measure (Trial 1 of the Test of Memory Malingering; TOMM). METHODS: TDS was compared to Digit Span accuracy (DS), using TOMM as a criterion measure, in a sample of 99 veterans with mTBI. Correlation and regression were used to characterize associations between PVTs. Logistic regression was utilized to examine the relationship between embedded PVTs and the odds of TOMM failure. Classification accuracy of TDS was examined using receiver operating characteristic (ROC) curves. Predictive power of TDS to estimate TOMM failure was calculated for the current sample and for hypothetical populations with common base rates (BRs). OUTCOMES: TDS significantly predicted failure on the TOMM and added greater incremental predictive value to the model compared to DS accuracy. Estimates of the predictive power of TDS were calculated using observed and hypothetical BRs. Sensitivity to stand-alone PVT, failure was 38% when specificity was set at 90%. CONCLUSION: TDS offers a promising embedded PVT method, given its strong convergence with an established stand-alone PVT.

The Role of Acetylcholine in Attention in Turtles (Chrysemys picta).

Research on mammals and turtles has suggested that acetylcholine is involved in attention in these groups. Two experiments investigated the ability of painted turtles (Chrysemys picta) to ignore irrelevant stimuli when the basal forebrain acetylcholine system was compromised. In experiment 1, turtles given lesions of the basal magnocellular cholinergic nucleus (NBM) or sham lesions were tested on a go/no go discrimination between horizontal and vertical stripes with or without irrelevant inserts in the box. The irrelevant inserts were blue and white checked walls and green carpet on the floor. The group with lesions of the NBM and no irrelevant inserts had no difficulty learning the task, but the lesioned group with irrelevant inserts was impaired on the discrimination. The sham-lesioned group was not impaired by the presence of irrelevant inserts. In experiment 2, turtles were given either the acetylcholine muscarinic receptor blocker scopolamine or saline and tested on the same task. The turtles given scopolamine had no difficulty learning the task in the absence of irrelevant inserts, but they were severely impaired when irrelevant inserts were present. The irrelevant inserts did not affect the learning of control turtles given saline. These findings provide evidence that acetylcholine enhances turtles' ability to orient to relevant stimuli and suggest that its role in learning and memory may be to allow animals to orient to the stimuli relevant to a task and to ignore irrelevant stimuli.

Population Base Rates and Disease Course of Common Psychiatric and Neurodegenerative Disorders.

Knowledge of population base rates of neurological and psychiatric disorders is fundamental for diagnostic decision making. Consideration of relevant probabilistic information can improve diagnostic efficiency and accuracy. However, such data continue to be misused or underutilized, which can lead to misdiagnoses and negative patient outcomes. The aim of the current review is to create an easily accessible and comprehensive reference of existing age of onset as well as prevalence and incidence data for common neurodegenerative and psychiatric disorders in adults. Relevant epidemiological data were compiled from well-respected and frequently-cited textbooks and scholarly studies. Reviews were collected from PubMed, and publicly-available sources were gathered from Google Scholar. Results are organized and presented in several tables and a figure, which can be used as a diagnostic guide for students and clinicians across healthcare disciplines.

Delirium Detection and Impact of Comorbid Health Conditions in a Post-Acute Rehabilitation Hospital Setting.

Misdiagnosis and under-detection of delirium may occur in many medical settings. This is important to address as delirium clearly increases risk of morbidity and mortality in such settings. This study assessed whether Veterans who screened positive on a delirium severity measure (Memorial Delirium Assessment Scale; MDAS) differed from those with and without corresponding medical documentation of delirium in terms of cognitive functioning, psychiatric/medical history, and medication use. A medical record review of 266 inpatients at a VA post-acute rehabilitation unit found that 10.9% were identified as delirious according to the MDAS and/or medical records. Of the Veterans who screened positive on the MDAS (N = 19), 68.4% went undetected by medical screening. Undetected cases had a higher number of comorbid medical conditions as measured by the Age-Adjusted Charlson Index (AACI) scores (median = 9, SD = 3.15; U = 5.5, p = .003) than medically documented cases. For Veterans with a score of 7 or greater on the AACI, the general relative risk for delirium was 4.46. Delirium is frequently under-detected in a post-acute rehabilitation unit, particularly for Veterans with high comorbid illness. The relative risk of delirium is up to 4.46 for those with high medical burden, suggesting the need for more comprehensive delirium screening in these patients.

Cognitive reserve and executive function: Effect on judgment of health and safety.

Individuals with the same neurological conditions do not necessarily manifest the same behavioral presentation, which suggests differences in resilience and vulnerability among individuals, a concept known as cognitive reserve. This study sought to explore the relationship among cognitive reserve, executive functioning, and health and safety judgment among a sample of older adult inpatients in an extended medical care unit at a Veterans Health Administration hospital. We hypothesized that cognitive reserve, as determined by an estimate of premorbid intellectual ability, would act as a protective factor against poor judgment in older adults with executive dysfunction. Participants included 200 Veterans who completed a comprehensive neuropsychological assessment, including measures of health and safety judgment, executive functioning, global cognitive functioning, and premorbid intellectual ability. After controlling for global cognitive functioning, executive functioning abilities did not have an effect on judgment abilities among those with high estimated intellectual ability. However, executive functioning had a significant effect on judgment abilities among those with low estimated intellectual ability. Our results suggest that intact executive functioning is critical for making appropriate health and safety decisions for patients with lower measured intellectual abilities and provide further support for the cognitive reserve model. Clinical implications are also discussed.

Dual-tasking gait variability and cognition in late-life depression.

OBJECTIVES: Studies have demonstrated an association between major depressive disorder (MDD) symptoms and fall risk in older adults, which may be at least partially mediated by executive functioning skills. There have also been observations of increased gait variability associated with fall risk and disease. This preliminary study first sought to understand whether gait variability in the context of dual task cost differs among older adults with MDD, relative to those with no history of psychiatric illness, and second, to identify relationships between gait variability measures and cognitive functioning in the context of MDD. METHODS: We recruited 15 older adults with MDD and 17 non-depressed (ND) community-dwelling older adults. All participants had impaired balance based on unipedal stance time. Assessments included neuropsychological measures and measures of gait variability using an instrumented gait mat (GAITRite© ) in the context of dual task relative to single task performance (i.e., dual task cost). RESULTS: The groups did not differ on any gait variability parameters. The MDD group demonstrated poorer performance in the psychomotor speed domain, relative to the ND group, but cognitive functioning between the groups in other domains was equivalent. In MDD, increased variability in stride time, stride velocity, and swing time during dual-tasking were associated with poorer executive functioning and visual memory. In ND, no significant relationships between gait variables and cognitive performance were observed. CONCLUSIONS: Findings suggest that unique cognitive mechanisms underlie mobility problems associated with fall risk in late-life depression.